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Biomedical subjects

R D Kimbrough

Publications and source records attributed to R D Kimbrough.

At least 19 recordsLinked to original sources
PubMed1995

Polychlorinated biphenyls (PCBs) and human health: an update.

Polychlorinated biphenyls (PCBs) are a mixture of 209 different chlorinated biphenyl congeners (forms) of which 36 are environmentally relevant. PCBs are lipid (fat)-soluble, stable compounds. PCBs may be contaminated with more highly toxic polychlorinated dibenzofurans (PCDFs). Some PCDFs were primarily responsible for the two poisoning outbreaks--Yusho and Yu-Cheng. Based on the reports on workers and the general population, no clear and convincing evidence that PCB exposures were casually associated with adverse health effects was advanced; this included cancer for a wide range of body burdens and exposures for serum PCB concentrations > 1000 ppb (micrograms/l) and adipose PCB levels > 400 ppm (mg/kg). No meaningful reproductive problems have been identified in female capacitor workers. In the opinion of the review author, the available evidence for cancer and for reproductive effects is inconclusive. Adverse neurobehavioral effects in infants and young children have been reported in a study of women in the general population and a study of fish eaters and their offspring. The adverse effects observed in the two studies were not the same; the exposure assessments in both studies are not well defined and have many uncertainties. Subhuman primates appear to be more sensitive to reproductive and other adverse effects of PCBs than humans. Obvious external clinical signs are observed in the offspring of subhuman primates at dosage levels below those experienced by female capacitor workers and members of the general population prior to the control of PCBs.

Animals↗
PubMed1994

Determining acceptable risks: experimental and epidemiological issues.

The extent to which results of experimental toxicology studies can be used to assess risk for humans varies. Administering high doses of chemicals to experimental animals may produce indirect adverse metabolic and nutritional effects, and metabolic pathways may differ at high and low doses. The rate of metabolism at high and low doses and the metabolic pathways of chemicals in different species are important for establishing the reasons for differences in species responses. Animal species best suited to serve as a surrogate for humans vary for different chemicals. For realistic risk assessments, more detailed information on the toxicokinetics of chemicals in humans is needed. As data are developed to link early biochemical changes with future disease, it is important to determine their predictive value. Our present expectations of using various biomarkers to predict future health outcomes may be unrealistic. More baseline data are needed to determine which biomarkers are expressions of exposure and which are predictors of future disease. It is also unclear how lifestyle affects most biomarkers.

Animals↗
PubMed1994

Management of children with slightly elevated blood lead levels.

OBJECTIVE: To determine whether counseling of parents reduced blood lead levels in their young children. PARTICIPANTS AND METHODS: A lead exposure study was conducted in the vicinity of a defunct lead smelter. A total of 827 volunteers including 490 children younger than 6 years participated in the study. The mean venous blood lead level in the 490 children was 0.33 mumol/L (6.9 micrograms/dL), with a range of 0.03 to 1.94 mumol/L (0.7 to 40.2 micrograms/dL). A total of 78 (16%) children had blood lead levels > or = 0.48 mumol/L (10 micrograms/dL). However, only 5 (1%) of the children had blood lead levels of > or = 1.21 mumol/L (25 micrograms/dL). The blood lead levels in this community were much lower than levels reported in earlier studies in many areas of the United States, when lead levels in air and in food were higher. Most houses in the study community were built before 1920 and had high lead paint levels. High levels of lead were also found in many house dust and soil samples. Intervention consisted of home visits and counseling of parents of children with blood lead levels of > or = 0.48 mumol/L (10 micrograms/dL). RESULTS: In children with initial blood lead levels of > or = 0.48 mumol/L (10 micrograms/dL) the blood lead test was repeated 4 months later. The arithmetic mean blood lead level 4 months later showed a decrease from 0.72 mumol/L (15 micrograms/dL) to 0.38 mumol/L (7.8 micrograms/dL). An additional blood sample was taken 1 year after the first sample in a subset of 30 children. These children showed a mean blood lead level of 0.43 mumol/L (9 micrograms/dL) at the 1-year follow-up, whereas their mean blood lead level at the 4-month follow-up had been 0.38 mumol/L (8 micrograms/dL). CONCLUSION: Educating parents proved a very effective tool. Further studies are needed in larger populations to evaluate the effectiveness of this approach.

Child, Preschool↗
PubMed1993

Acute toxicity of gasoline and some additives.

The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels.

Animals↗
PubMed1991

Consumption of fish: benefits and perceived risk.

Fish, a useful source of protein, may be polluted by microbes, natural toxins, and/or synthetic chemicals. However, based on a review of the U.S. General Accounting Office, "There does not appear to be a compelling case to implement a mandatory comprehensive federal seafood inspection program." Although earlier studies showed higher body burdens of polychlorinated biphenyls (PCBs) in populations who consumed a lot of fish from polluted waterways, a recent study refutes these observations. No information is available in the United States on the levels of polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) in anglers who consume a great deal of fish presumed to be contaminated by these chemicals.

Animals↗
PubMed1991

Non-specificity of clinical signs and symptoms caused by environmental chemicals.

1. A review of the scientific literature revealed that 220 environmental chemicals had caused documented systemic toxicity in humans. This number is relatively small compared to the large number of industrial chemicals in the environment. 2. A total of 149 of these chemicals were verified as neurotoxins, thus emphasizing the sensitivity of this target organ. Despite the exclusion of chemicals that cause airway irritation only, 99 chemicals caused adverse effects on the respiratory system. Toxicity to the liver, kidneys and blood forming organs was less frequent. 3. Most of the individual clinical effects had a very low specificity in cases of human intoxication. Of 80 major signs and symptoms, 17 had only a single documented chemical aetiology. However, the combination of two or more signs or symptoms was found to provide an improved guidance to aetiological diagnosis. The paucity of specific signs and symptoms is probably one of the reasons that only 220 environmental chemicals have been documented as causes of human disease.

Environmental Exposure↗
PubMed1990

Kashin-Beck disease: a cross-sectional study in seven villages in the People's Republic of China.

Kashin-Beck disease (KBD) is an endemic disease that occurs in certain parts of the People's Republic of China and in Russia. The etiology of the disease is unknown. Selenium deficiency, mycotoxins, and chelating agents such as humic acid and decaying plant material from walnut tree forests have been suggested as causal agents. The primary lesion of this disease is the selective coagulative necrosis of the hypertrophic chondrocytes at the base of the articular and growth plate cartilages. A cross-sectional study was performed in the People's Republic of China in 7 villages, to focus on information about life styles, food consumption, and environmental factors from the village population where the disease is endemic. A total of 425 children were examined, of which 71 children had KBD. Results of detailed food consumption data analyses showed that certain combinations of food substances high in protein had a protective effect. It was also found that the disease was twice as prevalent in onset in boys as in girls, in the 12-yr-old age group. The overall onset of illness in this group of children ranged from 4 to 13 yr. Either the joints of the fingers or one ankle was affected first. Many of these children also had discolored teeth. However, this finding was unrelated to KBD.

Adolescent↗
PubMed1990

How toxic is 2,3,7,8-tetrachlorodibenzodioxin to humans?

The tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) measured in different species are reviewed. Based on the correlation of tissue levels and a toxic response in different species, humans are less or no more susceptible to the toxic effects of TCDD than most of the laboratory animals that have been studied. Thus, the present exposure of the general population to environmental levels of TCDD are related compounds should not be of concern.

Animals↗
PubMed1987

Porphyrins and hepatotoxicity.

Human porphyrias are rare inborn disorders of porphyrin metabolism. Porphyria cutanea tarda is one such disorder, which may occur spontaneously after the ingestion of drugs and alcohol. This is the "constitutional" type and is associated with a deficiency of uroporphyrinogen decarboxylase in the liver. This constitutional type must be differentiated from the "acquired" type, which occurred in hundreds of people poisoned by hexachlorobenzene in Turkey. Morphological changes observed in the livers of animals and humans vary greatly. Porphyria cutanea tarda may be associated with very little liver pathology or with very pronounced changes, depending on the agent causing the porphyria. Usually, the liver has an increased iron load, and mitochondria contain a crystalline material.

Animals↗
PubMed1986

Characterization of pancreatic-type tissue in the liver of rat induced by polychlorinated biphenyls.

Pancreatic-type tissue induced in the livers of rats treated with polychlorinated biphenyls was characterized by transmission electron microscopy and high-resolution immunocytochemistry. The cells of pancreatic-type tissue were arranged as acini and in small groups. By electron microscopy the pancreatic-type tissue showed features very similar to normal pancreatic acinar tissue, such as well developed rough endoplasmic reticulum (RER), large numbers of mature zymogen granules, and a basally located nucleus. Protein A-gold imunocytochemical technique showed localization of amylase and trypsinogen over the zymogen granules and RER. These findings confirm that this tissue in the liver is morphologically and functionally identical to pancreatic acinar tissue.

Amylases↗
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↗