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Journal ArticleDOI

Light and electron microscope study of chlorobiphenyl poisoning. In mouse and monkey liver.

01 Nov 1970-Archives of Environmental Health (Taylor & Francis Group)-Vol. 21, Iss: 5, pp 620-632
TL;DR: Looking at the effects on mouse and monkey liver of long-term oral administration of chlorobiphenyls (CBP), characteristic lesions of liver cells were produced by administration of CBP.
Abstract: The effects on mouse and monkey liver of long-term oral administration of chlorobiphenyls (CBP), 1.5 mg/day or more, have been investigated at selected intervals by light and electron microscopy. H...
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Journal ArticleDOI
01 Jan 1973
TL;DR: The Toxicity of Polychlorinated Polycyclic Compounds and Related Chemicals: Critical Reviews in Toxicology: Vol.
Abstract: (1973). The Toxicity of Polychlorinated Polycyclic Compounds and Related Chemicals. CRC Critical Reviews in Toxicology: Vol. 2, No. 4, pp. 445-498.

293 citations

Journal ArticleDOI
TL;DR: PCB toxicity experiments revealed that mink are very sensitive to these compounds and that the lethal dose varied inversely with the chlorine content of the PCB's although only Aroclor 1254 exerted a detrimental effect on reproduction when fed at a low level (2 ppm) for 8 months.
Abstract: Experiments were conducted from 1968 to 1974 to investigate reproductive complications and mortality in mink fed Great Lakes coho salmon and to ascertain the effects of polychlorinated biphenyls (PCB's) on this fur bearer The results of mink feeding trials indicated that coho salmon, as such, were not responsible for the loss of reproduction in the adult, or the kit mortality Mink diets that contained other species of Great Lakes fish caused similar reproductive complications, but to a lesser degree Rancidity, mercury poisoning and chlorinated hydrocarbon pesticide contamination of the fish were all discounted as being responsible for the problem The clinical signs and lesions noted in mink that died while receiving diets that contained Lake Michigan coho salmon were very similar to those observed in mink fed on rations that contained supplemental PCB's These included anorexia, bloody stools, fatty liver, kidney degeneration, and hemorrhagic gastric ulcers Analyses of tissues from mink that died when fed 30% Lake Michigan coho salmon or 30 ppm supplemental PCB diets showed similar PCB residues PCB toxicity experiments revealed that mink are very sensitive to these compounds and that the lethal dose varied inversely with the chlorine content of the PCB's although only Aroclor 1254 exerted a detrimental effect on reproduction when fed at a low level (2 ppm) for 8 months The reproductive failure encountered in feeding mink Lake Michigan coho salmon and Aroclor 1254 was shown to be of a non-permanent nature

216 citations

Journal ArticleDOI
TL;DR: There is need for an integrated approach, consisting of epidemiologic studies on high risk groups in the general population and in persons occupationally exposed, as well as periodic assessment of PCB residues in man, his food, and feed supplies.
Abstract: PCB residues are found in biota all over the world. A biologic magnification of PCBs has been demonstrated in the food chain: plankton-fish-fish eating birds. A world map of the PCBs residues in biota and some of their biologic effects are given in this study. The biologic effects of PCBs are varied and may generally be explained by the induction or inhibition of the activity of a large number of enzymes, which upsets quantitatively, normal biochemical processes. Harm to reproduction, growth, development, defense systems, tissues, and organs appeared in susceptible organisms as a result of such changes or as a chain reaction to heterostases. The adverse health effects, observed in persons occupationally exposed and in those accidentally poisoned, point to the risk for the general population of an ever-increasing environmental pollution by PCBs. There is need for an integrated approach, consisting of epidemiologic studies on high risk groups in the general population and in persons occupationally exposed, as well as periodic assessment of PCB residues in man, his food, and feed supplies.

214 citations

Journal ArticleDOI
TL;DR: The effect of Aroclor 1254 on the liver was more pronounced than that of A RoClor 1260, and the epithelial component of adenofibrosis consisted of goblet cells and cells that resembled the epithelium which lines the bile ducts.
Abstract: Male and female Sherman strain rats were fed polychlorinated biphenyls Aroclor 1260 and Aroclor 1254 at 0, 20, 100, 500 and 1,000 ppm in their diet. Rats received the dietary levels for eight months. Light microscopic changes consisted of hypertrophy of the liver cells, inclusions in the cytoplasm, brown pigment in Kupffer cells, lipid accumulation, and, at the higher dietary levels, adenofibrosis. Ultrastructural changes of the livers of exposed animals consisted of an increase in smooth endoplasmic reticulum and atypical mitochondria. Lipid vacuoles were occasionally surrounded by concentric membranes. The epithelial component of adenofibrosis consisted of goblet cells and cells that resembled the epithelium which lines the bile ducts. In general, the effect of Aroclor 1254 on the liver was more pronounced than that of Aroclor 1260.

171 citations

Journal ArticleDOI
TL;DR: Whether or not BHT acts as a carcinogen in long-term administration may depend not only upon the organ system examined, but also on the strain of the animal used.
Abstract: The anti-oxidant food additive, butylated hydroxytoluene (BHT), was fed to Sprague-Dawley rats at three concentrations: 0.2%, 0.4% and 0.8% for periods of 6, 12, 18 and 24 weeks, and the results were compared with corresponding groups treated with a potent carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA) groups, with olive oil, and with untreated control groups. BHT resulted in a significant increase in liver weight. The liver cells presented gradual vacuolization, cytoplasmic disintegration, "moth-eaten" appearance, ballooning degeneration, hepatocellular necrosis, aggregation of chromatin material around the periphery of the nuclear envelope, SER proliferation, RER clumping with broken cisternae, withered and autolyzed mitochondria, augmentation of lipid droplets and glycogen depletion. On the other hand, there was no sign of tumorigenicity. Whether or not BHT acts as a carcinogen in long-term administration may depend not only upon the organ system examined, but also on the strain of the animal used.

160 citations


Cites background from "Light and electron microscope study..."

  • ...mice and monkeys (Nishizumi, 1970) or even after 3 months, as in toad (Sadek and Abdul-Salam....

    [...]

References
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Journal ArticleDOI
TL;DR: Epoxy embedding methods of Glauert and Kushida have been modified so as to yield rapid, reproducible, and convenientembedding methods for electron microscopy.
Abstract: Epoxy embedding methods of Glauert and Kushida have been modified so as to yield rapid, reproducible, and convenient embedding methods for electron microscopy. The sections are robust and tissue damage is less than with methacrylate embedding.

9,741 citations

Journal ArticleDOI
TL;DR: Certain hitherto unobserved details are revealed and some sort of specificity exists, although the factors involved are not yet understood.
Abstract: Heavy metals may be incorporated from solution into tissue sections for electron microscopy The resulting increase in density of the tissue provides greatly enhanced contrast with minimal distortion Relative densities of various structures are found to depend on the heavy metal ions present and on the conditions of staining Certain hitherto unobserved details are revealed and some sort of specificity exists, although the factors involved are not yet understood

4,040 citations

Journal ArticleDOI
TL;DR: Among several heavy metal salts tested, the above-ment ioned " lead hydroxide" of Watson seemed to be the most effective in "s ta in ing ." Exper iments with the commercial ly available product showed that this salt would give no impregna t ion when dissolved in water, or in Institute.
Abstract: Meta l impregnat ion , or "s ta in ing ," of tissue sections for electron microscopy has become the accepted practice in recent years. Salts of metals of h igh atomic weight such as u ran ium, chromium, thor ium, lead, or tungsten, among many tested, have been found suitable (6, 1). "Lead hydroxide ," as prepar ted by Watson (6), is now widely used, hu t this solution is extremely unstable in air and becomes covered by a meta l l ic-appear ing film which imparts to the " s ta ined" section a well known deposit of e lectron-opaque particles and crystals, reducing considerably the percentage of clean areas suitable for micrography (Fig. l) . Several procedures and devices have been described to lessen these contaminat ions. Peachey (5), using lead hydroxide, or subacetate, found tha t if the solution is kept in a syringe with the protect ing cap filled with sodium hydroxide to absorb the CO2 of the atmosphere, con tamina t ion is reduced. More recently, a fairly unwieldy appara tus has been suggested for the same purpose (4). Tests performed in our laboratory in which " s t a in ing" was a t tempted in a chamber under cont inuous ni t rogen flow and in the presence of a ba r ium chloride t rap were not completely successful, which is to say tha t con tamina t ion cont inued to be a problem. A n u m b e r of o ther var iat ions have been recommended. Lever (2), e.g., described a method for prepar ing a " s t a in ing" solution by adding potassium hydroxide to a lead hydroxide solution. To dissolve some of the occasionally formed crystals of contamina t ion , the sections are rinsed afterwards for a few seconds in a weak potassium hydroxide solution; this step is very critical because the "s ta in ing" is also weakened by the alkali and uni form staining is difficult to achieve. These various shortcomings of current ly avai lable methods have st imulated us to search for a lead salt tha t would not be affected by the components of the atmosphere. Among several heavy metal salts tested, the above-ment ioned " lead hydroxide" of Watson seemed to be the most effective in "s ta in ing ." Exper iments with the commercial ly available product showed that this salt would give no impregna t ion when dissolved in water, or in Institute. Dr. Millonig's present address is Biological

1,310 citations

Journal ArticleDOI
TL;DR: A technique for staining sections of osmium-fixed, epoxy-embedded tissues for light microscopy using aqueous toluidine blue at pH 11.1 and does not require prior removal of embedding medium, which permits better utilization of the full resolving power of the light microscope.

800 citations

Journal ArticleDOI
TL;DR: The search for a medium which might offer improvements from the point of view of stability and buffering capacity for Palade's buffered osmic fixative was focused on s-collidine, which has a pK of about 7.4.
Abstract: In 1952 Palade introduced the use of Michaelis' veronal-acetate buffer for regulating the pH of osmium tetroxide-fixing solutions for electron microscopy (1, 2). This buffer has enjoyed wide popularity and is regarded as satisfactory by many cytologists. The veronal-acetate buffer suffers from several limitations, however. I t is not particularly stable, since it supports the growth of mould or bacteria. Hence it is not practical to make up large amounts in bulk nor to store it over a considerable period of time. I t is not possible to make up a solution much more concentrated than that recommended by Palade, which approaches saturation for veronal (diethyl barbituric acid). The veronal-acetate mixture was developed by Michaelis (3) to meet the need for a relatively non-toxic buffer system capable of broad pH range and constant ionic strength. For this it works very well. I t is actually two buffer systems in one; i.e., sodium acetate-HCl and sodium veronal-HC1. The former is most efficient between pH 4.2 and 5.2 (pK for acetic acid is 4.76), but is nearly inoperative at pH 7 to 8. The veronalHCI system is most efficient between pH 7.5-8.5 (pK for veronal is 7.96 (4)). As recommended by Palade, osmium tetroxide is most commonly used at pH 7.2-7.5. At these pH's the veronal-HC1 system is operating at the acid edge of its range, where it is not very efficient in suppressing changes toward further acidity (2). Thus the combined veronal-acetate buffer system is not particularly effective in the pH region between its two buffer systems, namely between pH 5.2 to 7.5. This has been confirmed by titration curves. Even though our experience with Palade's buffered osmic fixative has been satisfactory, we undertook a search for a medium which might offer improvements from the point of view of stability and buffering capacity. Our attention was focused on s-collidine ('y-collidine or 2,4,6-tr imethylpyridine), which has a pK of about 7.4 (7.37 in

689 citations