In two complete replicates of a 2 × 2-fractorial-designed experiment involving chlorobenzene and γ-hexachlorocyclohexane (lindane), the hepatotoxicity induced by a challenge dose of chlorobenzene was altered by the pretreatments due to selective changes in various metabolis pathways. Pretreatment with either toxicant, alone or in combination, elevated the relative metabolism of 1.12 g chlorobenzene/kg to conjugated and polar metabolites. The relative importance of these pathways was increased most by pretreatment with chlorobenzene + lindane and least with chlorobenzene. The incidence and severity of chlorobenzene-induced hepatocellular necrosis was dependent on how much the pretreatments increased excretion of these metabolites relative to that of p-chlorophenol, since the conjugates and polar metabolites represent an inactivation of the toxic chlorobenzene-3,4-epoxide whereas p-chlorophenol reflects its formation. Thus these changes in the metabolic pathways resulted in either (i) a marginally significant decrease in hepatotoxicity (chlorobenzene pretreatment); (ii) significant reduction in both the incidence and severity of the lesions (lindane pretreatment); or (iii) absence of centrilobular hepatocellular necrosis in all but 1 of 12 rats where a minimal degree of necrosis was present (chlorobenzene + lindane pretreatment). In this study, the effect of pretreatment with xenobiotics on chlorobenzene-induced hepatotoxicity was dependent on how much the pretreatments altered the inactivation of chlorobenzene-3,4-epoxide relative to its formation.

Adult male rats were fed diets containing 0, 5, 15, and 30 ppm chlordecone for 90 d and then either bred to untreated females or sacrificed for terminal studies. Chlordecone residues in liver, fat, and serum were determined in the treated males. Reproductive performance was unaffected, and no histologic changes in the male sex organs could be attributed to chlordecone treatment. Reversible decreases in the motility and viability of epididymal spermatozoa and decreased sperm reserves in the cauda epididymidis were observed in rats fed 15 or 30 ppm. No effect on sperm morphology or on sperm concentration in epididymal fluid was detected. Chlordecone accumulation in tissues was linearly related to dietary levels, with the highest chlordecone concentration occurring in the liver.

Female Sprague-Dawlwy CD rats were fed 0, 60, 80, 100, 120 and 140 ppm hexachlorobenzene (HCB) continuously in the diet and 2 successive litters raised. These doses were selected to range from approximately the no observable effect level to lethality in suckling offspring of treated dams. In the F1a generation, the 21-day mortality was 9.2, 19.8, 30.0, 45.4, 93.1 and 92.6% in offspring of dams fed 0, 60, 80, 100, 120 and 140 ppm HCB, respectively. In the F1b generation, a similar mortality of 18.5, 21.5, 19.5, 45, 100 and 94.1% was observed at these 5 dose levels, respectively. The neonatal lethality observed was related to both maternal dose of HCB and the cumulative lactational exposure. Clinical signs of maternal toxicity were not observed and fertility and fecundity were unaffected. In the lungs of HCB treated dams, increased numbers of intraalveolar foamy histiocytes and hypertrophy and proliferation of the lining endothelial cells of pulmonary venules were observed. These microscopic findings of pulmonary effects of HCB confirmed previous findings of this laboratory.

The early histologic lesions and sequential changes in the development of mirex-induced cataracts were studied in the offspring of lactating female Sherman rats given oral doses of mirex for 5 consecutive days post partum. The earliest histologic change, seen at neonatal day 7, was slight swelling of the individual cortical lens fibers. At day 9, many swollen but intact fibers were observed, and at days 11 and 13, extensive degeneration and necrosis appeared throughout the cortex of the affected lenses.

Oral LD50 values for pentachlorobenzene (QCB) in rats were 1125, 1080, and 940 mg/kg for adult males, adult females, and weanling females, respectively. The oral LD50 values in mice were 1175 mg/kg for males and 1370 mg/kg for females. Clinical signs of toxicity included tremors and narcosis. Dermal application of 2500 mg/kg did not produce clinical signs in rats. In subchronic studies weanling male rats were fed 0, 125, or 1000 ppm QCB for 100 days and weanling females fed 0, 125, 250, 500, or 1000 ppm for 180 days. No clinical signs of toxicity or effects on growth were observed in these rats throughout the exposures. QCB accumulated in adipose tissues at approximately 1.5-2.2 times the dietary concentrations. Porphyrin measurements were made only in females. Terminal values for urinary uro-and coproporphyrin and accumulation of liver porphyrins were not remarkably different in control and QCB-treated groups. In groups fed 1000 ppm, the WBC was increased and red blood cell indices were generally decreased compared to controls. The rats were pair-bred with untreated partners after 67 days of treatment. Fertility and fecundity were unaffected in either sex; however, suckling pups of QCB-treated mothers fed 250 ppm or more developed tremors and at 1000 ppm most died before weaning. Adrenal weights in males and kidney weights in both sexes were increased in adults fed 1000 ppm. In groups fed 250 ppm or more liver/body weight ratios were increased in both adults and in weanling offspring of QCB-treated dams. Hepatocellular enlargement was particularly evident in the 500 and 1000 ppm groups. In the kidneys of adult males, more numerous and larger foci of tubular atrophy and lymphocytic infiltration were seen at 1000 ppm than were seen in controls and dose-related increases in hyaline droplet formation occurred at 125 and 1000 ppm.

The fetotoxic potential of mirex in the rat and the cataractogenic potential of mirex and Kepone in the rat and mouse have been studied. Signs of fetal toxicity including edema, undescended testes, and reduced weight were seen in litters of CD rats treated with 7 mg/kg/day of mirex on Days 7–16 of gestation. The postpartum administration of mirex to both rat and mouse dams resulted in dose-related incidences of irreversible cataracts. Outlined lenses were also noted in pups in treated litters. A total dose of 10 mg/kg mirex administered either singly or over 4 days during the first week after birth was cataractogenic in both albino (CD, Sherman strains) and nonalbino (Long-Evans) rats. A total dose of 12 mg/kg was cataractogenic in the CD-1 mouse. Cataracts were present by Day 13 (eye-opening) in the rat pups and generally appeared after Day 20 in the mouse. The maternal administration of mirex also resulted in dose-related decreases in weight and viability in their litters. The postpartum administration of Kepone to maternal rats and mice did not result in any alterations in the lenses of the pups.

Female rats were fed 30, 100, 300, and 1000 ppm of pure and technical grades of hexachlorobenzene (HCB) for 1 week and 30, 100, and 300 ppm of each for 4 months. Technical HCB was contaminated with 200 ppm decachlorobiphenyl and 4 ppm octachlorodibenzofuran but contained no other chlorinated dibenzofurans or dibenzo-p-dioxins (<0.5 ppm). Pure HCB contained 0.5 ppm decachlorobiphenyl but no detectable amount of any chlorodibenzo-p-dioxins. Pure and technical HCB increased aryl hydrocarbon hydroxylase, aminopyrine N-demethylase, cytochrome P-450, glucuronyl transferase, and liver/body weight ratios comparably at each dose level. Neither grade of HCB shifted the peak of the CO-difference spectrum or altered the 455:430 ratios of the ethyl isocyanide difference spectra appreciably. Livers, lungs, adrenals, and hearts were evaluated histologically. Enlargement of liver cells was seen at 100 and 300 ppm HCB. Marked hypertrophy and proliferation of the lining endothelial cells of the smaller pulmonary blood vessels was observed in rats fed 100 and 300 ppm HCB. At 100 ppm, the number of affected vessels was usually greater in rats fed technical HCB than in those fed pure HCB. At 300 ppm, the pulmonary effects of pure and technical HCB were identical. The porphyria, cutaneous lesions, hyperexcitability, changes in liver enzymes, and morphological changes in the liver were identical in rats fed pure and technical HCB at all dose levels, indicating that these changes were produced by HCB, rather than chlorinated dibenzofuran or dibenzodioxin contaminants.

The introduction of minced, Rous sarcoma virus-treated chicken embryonic tissue into the brains of conditioned rats is followed by the development of typically appearing Rous sarcoma. Such tumors are not seen in rats which receive virus alone or which are implanted with uninfected embryonic tissues. A requisite for optimum tumor growth is conditioning by both x-radiation and cortisone. Animals conditioned by x-ray alone show poorer tumor response. Nonconditioned rats or those treated with cortisone alone rarely develop Rous sarcoma.

THE brain has been employed in this laboratory as a site for the transplantation of malignant cells from tissue culture to rat1, and such transplantations are proving useful for both oncological and virological investigations. On the assumption that this procedure may also provide a new approach for the study of the nature and mechanism of alterations occurring in cells grown in vitro it was decided to apply the procedure to normal monkey cells grown in tissue culture.

Journal Article Basophilic (Mucinous) Degeneration of the Myocardium Get access Thomas M. Scotti, M.D. Thomas M. Scotti, M.D. Department of Pathology, University of Miami School of Medicine, Coral Gables, Florida, and Jackson Memorial Hospital, Miami, Florida Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 25, Issue 9, 1 September 1955, Pages 994–1011, https://doi.org/10.1093/ajcp/25.9.994 Published: 01 September 1955 Article history Received: 04 April 1955 Accepted: 06 June 1955 Published: 01 September 1955

A case of carcinoid (argentaffinoma) in a Meckel's diverticulum, which was found incidentally at autopsy and showed no metastasis, is reported and six other instances of this situation were found in the literature.

Examples of carcinoid (argentaffinoma) occurring in Meckel's diverticulum are uncommonly reported in the literature.The first proven case was recorded by Stewart and Taylor 1 in 1926.These authors stated that the one presented by Hicks and Kadinsky 2 in 1922 was "one of heterotopia of gastric mucosa and not a carcinoid tumor."This opinion was based on their examination of tissue sent to them by Dr. Hicks.In 1935, Price 3 published another instance of argentaffinoma in Meckel's diverticulum and Hertzog and Carlson 4 added two more cases.Collins et al. 5 summarized the above cases in 1938 and reported one of their own.Ashworth and Wallace,6 in 1941, recorded three carcinoids, one of which was in a Meckel's diverticulum.Thus, we have been able to find only six acceptable instances of argentaffinomas in this congenital anomaly.Because of the rarity of this situation, the following case is being presented.RE PORT OF A CASE J. W., a 68 year old white man, entered the Medical College of Virginia Hospital with a his tory of diabetes mellitus, hypertensive cardiovascular disease, and both old and recent cerebrovascular accidents.He died three weeks after admission from bronchopneumonia.Incidentally at autopsy a Meckel's diverticulum was found in the terminal ileum a short distance (about two feet) from the ileocecal valve.It 'measured approximately 3 cm. in length and 1 cm. in greatest diameter.Externally nothing unusual was seen so it was left intact and fixed in 10 per cent formalin .After fixation, it was opened and a discrete yellow nodule, wh ich measured 6 mm. in greatest dimension, was no ted in the submucosa near the tip of the diverticulum.The overlying mucosa was intact.A resistance was feit on sectioning through the nodule.Microscopically the mass was found to be a small tumor lying between the mucosa and muscularis but partially infiltrating the former.(See fig. 1, 2, and3) The neoplasm consisted of varying sized and shaped nests and cords of cells in a fairly cellular fibrous tissue stroma.These cells had an indistinct border, a clear to faintly acidophilic cytoplasm and large vesicular basophilic spherical nuclei.The nucleoli were not prominent and no mitotic figures were seen.A small nu mb er of lymphocytes and macrophages infiltrated the stroma.One small questionable area of infiltration into the muscularis