Showing papers in "Critical Reviews in Toxicology in 1982"

The route and significance of endogenous synthesis of alkaloids in animals.

Abstract: There is now substantial evidence that several TIQs and beta-carbolines are present in vivo and increase during certain pathological conditions. It still remains to be determined, however, precisely what roles they play in endogenous functions and whether or not they are critical for the expression of these pathological conditions. Accumulating biochemical information continues to support the notion that these compounds can act as false transmitters. The exciting new findings, which will certainly receive a great deal more attention, concern the interaction of some of the beta-carbolines with the benzodiazepine receptor. Determining if a beta-carboline is an endogenous receptor ligand will attract further research interest on the theoretical and specifically clinically-directed levels. Biochemical, morphological, and behavioral data indicate that some of the condensation products can act as neurotoxins. Very few experiments have included an examination of long-term effects of exposure to one of these alkaloids, so the amount of information on this issue is limited. Chronic rather than acute administration of an alkaloid is more likely to mimic the pathological states in which these compounds are hypothesized to play a role. Biochemically, both the dopaminergic and serotonergic systems have been shown to be affected by chronic treatments with certain alkaloids. Progressive and long-term behavioral alterations also have been reported. Such changes may reflect an adaptation to an increase or decrease in activity of particular systems or a neurotoxic action.

Capsaicin--a literature survey.

Abstract: (1982). Capsaicin — A Literature Survey. CRC Critical Reviews in Toxicology: Vol. 10, No. 4, pp. 321-339.

The toxicology of cocoa and methylxanthines: A review of the literature

Abstract: The critical review of the literature cited on pharmacology, toxicology, metabolism, and safety assessment clearly demonstrates that cocoa per se has not attracted a great deal of scientific interest because of its long-term usage with no reported adverse effects that would be injurious to man. On the other hand, a great deal of research has been directed towards understanding the pharmacological properties of the methylxanthines--caffeine, theobromine, and theophylline. Much of the emphasis on metabolism, toxicology, teratogenic potential, and safety assessment has been on the evaluation of caffeine. In light of the serious health concerns ascribed to the effects of caffeine and the lack of basic information on theobromine and theophylline, it is imperative that a major research program be undertaken to evaluate these methylxanthines and, of course, cocoa, coffee, and tea. It only will be through elucidating their mechanism of action that we will be in a position to assess their safety. Before committing research efforts to evaluating the long-term effects of these methylxanthines and their respective foodstuffs, which serve as our primary source of exposure, it is critical to initiate more basic research on the metabolism of caffeine, theophylline, and theobromine in several animal species and man. While published reports do appear in this area, it is essential to understand fully the similarities and differences between various animals and man. The influence of dietary factors and drug interactions must also be determined. Before establishing dosage levels for a chronic toxicity study, the pharmacokinetics of the dose must be determined in the species that will be used in long-term studies. This is necessary if there is a dose-dependency in the animal above which saturation may occur and the plasma half-life kinetics change, or shifts occur either in the metabolic pathways of degradation and/or in the route of excretion from the body. The area of teratology must also be thoroughly evaluated. Studies undertaken should include identification and quantitation of the metabolites of caffeine, theophylline, and theobromine in the pregnant animal, the respective pharmacokinetics of each compound, dose-dependency (if this is the case), and their potential teratogenicity. In addition, the influence of other drugs or dietary variables must be included. In addition to teratology, a great deal of research is needed to assess and quantitate fetal and neonatal metabolism of these compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

A Critical Review of the Literature on Nitrobenzene Toxicity

Abstract: This literature review encompassing information available through 1980 and limited coverage in 1981, emphasizes results useful in assessing the potential toxic effects of nitrobenzene to man. Nitrobenzene exposure in man or experimental animals is most often associated with methemoglobinemia. Histopathologic changes also are observed in the hemato-lymphoreticular system, central nervous system, and liver. In addition, lesions have been reported in adrenals and testes. No information was found on carcinogenic or teratogenic potential, fertility, or reproductive effects of nitrobenzene. Results from Ames Salmonella assay are negative but test procedures are questionable; metabolites give positive results. Metabolism of nitrobenzene involves either oxidation or reduction yielding p-aminophenol and p-nitrophenol, and other reduced intermediates. From the foregoing, several aspects of nitrobenzene toxicity have been identified which warrant further study. Recommendations are made for chronic and subchronic exposure of test animals via inhalation to assess various toxicological endpoints. In addition, the relationship of nitrobenzene metabolism to its toxicity needs to be established. Genotoxic effects of nitrobenzene also need study.

The Mesothelium and Its Reactions: A Review

Abstract: The origins, nature, and reactions of the mesothelium have intrigued investigators for over 100 years. Recently, the use of sophisticated techniques has clarified earlier impressions of its development, structure, and function. The structure of mesothelium reflects its functional properties, its long slender microvilli entrapping a layer of glycosoaminoglycans, providing a frictionless free surface between the parietal and visceral serosa. Transport requirements are met by various surface modifications and both inter- and intra-cellular mechanisms occur. The presence of stomatal openings in the mesothelial membrane has been established, and they may have a major role to play in the movement of cells to and from the serosal cavities. In addition, mesothelial cells can respond to situations of increased functional demand and during the course of inflammation, the mesothelium's fibrinolytic properties are of major importance in preventing the formation of adhesions and the enhancement of healing. Of all the unanswered questions the most significant is the nature, localization, and potentialities of mesothelial precursors. A mesodermal origin is readily acknowledged, but the healing process of damaged mesothelium is less clear. It seems probable that "mature" mesothelium is one source of cell renewal, but mesenchymal cells located in the submesothelial serosa are also strong contenders. Neoplastic mesothelium can adopt a spectrum of histological appearances, reflecting its mesodermal origins. In fact, overacceptance of this concept has erroneously led to the classification of other neoplasms arising in the serosal area as mesotheliomas. Although the ocogenic sequence is still obscure, asbestos is recognized as the major etiologic agent in malignant mesotheliomas. In 1955, Hartwell described differing impressions of the peritoneum as seen through the eyes of an anatomist, an histologist, and a surgeon. In this review on the mesothelium we have attempted to unravel some of its complexities as viewed by embryologists, electronmicroscopists, cell biologists, pathologists, and oncologists.

Phencyclidine (PCP): a review and perspectives.

Abstract: (1982). Phencyclidine (PCP): A Review and Perspectives. CRC Critical Reviews in Toxicology: Vol. 10, No. 2, pp. 145-177.

Passage of Chemicals into Human and Animal Semen: Mechanisms and Significance

Abstract: This review will begin with a brief account of the secretory mechanisms operating in the male reproductive tract. The entry of the different chemicals will be dealt with; with separate reference to testicular fluids, epididymal plasma, prostatic and vesicular secretions, and whole semen. Examples will be given of a number of chemical substances capable of passing into the secretions of the male reproductive tract and semen, in man and in animals--antispermatogenic and antiandrogenic agents, industrial chemicals, chemotherapeutic drugs, food additives, etc. The review will end with a critical appraisal of the methods involved and the results obtained from analyses of various chemicals in semen.

Immunotoxicology of silica

Abstract: (1982). Immunotoxicology of Silica. CRC Critical Reviews in Toxicology: Vol. 10, No. 4, pp. 303-319.

Tumors in Control Hamsters, Rats, and Mice: Literature Tabulation

Abstract: (1982). Tumors in Control Hamsters, Rats, and Mice: Literature Tabulation. CRC Critical Reviews in Toxicology: Vol. 10, No. 1, pp. 49-79.

The effects of nitrous oxide on cobalamins, folates, and on related events

Abstract: The anaesthetic gas nitrous oxide (N2O), when inhaled for longer than 6 hr, produces megaloblastic anemia in man. Longer term inhalation, as in addicts, produces a syndrome similar to that due to B12 neuropathy, and long term exposure to low concentrations results in an increased abortion rate and neuropathy, particularly in dental personnel. N2O acts by oxidizing vitamin B12 from the active reduced cob[I]alamin form to the inactive cob[III]alamin form. In turn, this inactivates the enzyme methionine synthetase which requires both B12 and folate as cofactors. In the rat, hepatic methionine synthetase is completely inactivated after 3 hr exposure to a mixture of equal parts of N2O/O2. There is an impared uptake of folate analogues by the liver so that the plasma folate level rises and thereafter there is a considerable loss of folate into the urine. Hepatic folate concentration falls to 25% within 10 days of N2O exposure. There is a failure to synthesize folate polyglutamate (the active folate coenzyme) from all other than formyltetrahydrofolate. As oxidization of the methyl of methionine is an important source of formyl, the failure of methionine synthesis in turn appears to lead to the failure in supply of formate and, hence, a lack of the formylfolate substrate.

Behavioral Toxicology in Risk Assessment: Problems and Research Needs

Abstract: Behavioral methods are being used with increasing frequency in toxicology to assess the deleterious effects of chemicals to which we are exposed. The impetus for the use of behavioral techniques in risk assessment resulted from the presumption that they were more sensitive than other tests in detecting toxicity. A more logical reason for the use of behavioral tests is the fact that behavior is the functional indicator of the net sensory, motor, and integrative processes occurring in the central and peripheral nervous system. Thus, the functional capacity of the nervous system cannot be determined independent of behavioral analysis. Some of the problems confronting behavioral toxicology are (1) the translation of human subjective complaints into behavioral tests in animals; (2) determining subtle effects on the nervous system in the face of the well-known functional reserve and adaptability of the system; (3) dealing with the variety of statistical problems resulting from the use of multiple tests, multiple measurements using the same test and the (relatively) large variability inherent in some behavioral phenomena; and (4) selecting the proper tests. Three critical research needs in behavioral toxicology as they relate to risk assessment are (1) development and validation of methods, (2) determining subpopulations atmore » greatest risk, and (3) developing a strategy for determining interactions between two or more agents.« less

Quantitative morphological studies of neuropathological changes. Part 1.

Abstract: Quantitation of morphological changes in the nervous system is valuable for demonstrating different regions and cell types involved in a pathological process. Quantitative anatomical studies are numerous, whereas quantitations of pathological conditions are relatively few. This seems to be due partly to technical difficulties arising when comparing normal with pathological brain tissue. Shrinkage of the whole brain or of substructures is important but difficult to determine, and earlier studies are often inaccurate due to lack of precise measurement of this parameter. This review deals with three different technical aspects: (1) measurements at the macroscopical level, (2) the light microscopical morphometry, and (3) the stereological principles which are used primarily in electron microscopical quantitation. The most used techniques and formulas are reviewed in order to give an impression of the possibilities and requirements in quantitative neuropathology. After each of the major areas, macroscopical measurements, determination of nuclear and cell size and nuclear number, vascular network, and stereology, a few practical comments are given as well as references for further information on the topic. The quickly developing electronic image analysis is dealt with in the section on capillary network measurements and in the last, concluding section.

Effects of Power Plant Coal Pile and Coal Waste Runoff and Leachate on Aquatic Biota: An Overview with Research Recommendations

Abstract: Coal, the major energy reserve in the US, accounts for nearly 80% of the known attainable resources and 74.0% of the ultimate recoverable reserves.’ In 1975 the US. produced 19% of the world supply of bituminous and lignite coals with approximately 73% of this coal consumed by the electric utilities.2 Gordon3 has reported that the use of coal for electric power generation will likely increase in future years in order to achieve our national goal of energy independence. The increased use of coal will result in the production of large quantities of fly ash, scrubber sludge, and other coal waste disposal products. Storage of this coal waste in disposal piles along with coal storage piles causes potential problems for aquatic biota that may be subjected to runoff and leachate from these piles entering aquatic systems. It has been well documented that runoff and leachate from coal piles and waste disposal piles contain a complex mixture of metals, salts, and organics. During independent studies various investigators have reported that ar~enic,~ cadrni~m,~ and selenium6 are important components of coal pile and coal waste effluents that could cause potential biological problems in the aquatic environment near coal-fired power plants. For this reason, we have selected these metals for the focus of this review. Recently the US. Environmental Protection Agency reviewed the toxicity literature on these metals.’-’ Therefore, this review was not intended to duplicate those reviews, but rather to present studies addressing actual concepts regarding the occurrence and toxicity of these metals relevant to coal pile and coal waste disposal effluents. The emphasis of the review was (1) to evaluate studies regarding the occurrence and toxicity of the above metals associated with coal effluent and (2) to identify areas not adequately addressed in the existing data. Data for both fresh and tidal fresh/oligohaline invertebrates and fish were evaluated. An attempt was initially made to determine the combined interactive effects of arsenic, cadmium, and selenium. However, it became evident from a preliminary review of the literature that suitable data and models were not available to predict the collective toxicity of these metals based on the individual toxicity of each Therefore, we reviewed the toxic effects of each metal separately. The following terms and subsequent definitions are used throughout the paper: bio

Power plant chlorination effects on estuarine and marine organisms.

Abstract: (1982). Power Plant Chlorination Effects on Estuarine and Marine Organisms. CRC Critical Reviews in Toxicology: Vol. 10, No. 1, pp. 27-47.

Immunology of hypersensitivity pneumonitis.

Abstract: Hypersensitivity pneumonitis (extrinsic allergic alveolitis) represents a spectrum of granulomatous, interstitial, and alveolar-filling lung disorders of which farmer's lung is a classic example. A major source of offending antigens in these diseases are thermophilic actinomycetes growing in moldy vegetable matter especially Micropolyspora faeni, and members of the Thermoactinomyces genus. Acutely, hypersensitivity pneumonitis presents as cough, dyspnea and fever, with crepitant rales, leucocytosis, diffuse interstitial and alveolar pulmonary infiltrates and a restrictive-type pulmonary functional deficit. Symptoms usually begin 4 to 6 hr after exposure to large quantities of causative organic dust. Chronically, these diseases may present with the gradual onset of cough, dyspnea on exertion, fatigue, anorexia, and weight loss which may progress to pulmonary fibrosis or severe pulmonary insufficiency. While early ideas on the pathogenesis of hypersensitivity pneumonitis support the role of Type III immune complex hypersensitivity, more recent evidence attests to the important and integral role of Type IV or delayed-type hypersensitivity. It is the purpose of this review, therefore, to describe those immune mechanisms relevant to the pathogenesis of hypersensitivity pneumonitis and stress the importance of "local" pulmonary immune responsiveness.