Journal of environmental pathology and toxicology最新文献

Exposure of mice to sodium arsenate (Na2HAs04) at levels of 2.5, 25 and 100 ppm As in the drinking water for 10-12 weeks increased the latent period and decreased the incidence of tumors induced by injection of MSB sarcoma cells. Tumor growth and regression induced by Moloney sarcoma virus (MSV) was not significantly affected by arsenic exposure. Cell mediated tumor immunity was either unaffected or enhanced by exposure to arsenic. Our results indicate that chronic exposure to sodium arsenate at arsenic levels as high as 100 ppm is not detrimental to mice in terms of tumor growth and immunosuppression.

The Mallard duck (Anas Platyrhynchos) is the waterfowl model of choice for testing the reproductive impairment of pesticides and environmental contaminants. The literature contains numerous reports on the effects of pesticides on egg shell development for mallards, quail and other avian species. Limited control data for reproductive evaluation of pesticides can be found. This paper summarizes one generation reproduction results from 75 control female mallard ducks. One male and five female adult ducks were housed in clean pens with tap water and game bird breeder ration available ad libitum. The pre-egg laying cycle was ten weeks in duration. For the first eight weeks, the photoperiod was seven hours light per day, after which the photoperiod was increased to 17 hours to induce egg laying. Eggs were collected daly for eight weeks and incubated. Shell thickness was measured on one egg from each pen bi-weekly. The mean reproductive indices are as follows: Eggs Cracked/Eggs Laid - 2.18%; Viable 11-Day Embryos/Eggs Set-85.2%; Live 21-Day Embryos/Viable 11-Day Survivors-97.6%; Hatchlings/Live 21-Day Embryos-80.6%; and 14-Day Survivors/Hatchlings-89.3%. The mean egg shell thickness for 60 eggs is 0.378 millimeters.

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.

Review of the recent literature indicated, that the general interest in anatomic pathology is declining and the value of "routine" autopsies is debated, since they disclose merely different degrees of degenerative changes, without any explanation as to their possible causes. Today it is an accepted fact, that rapid changes in man's environment represents a serious health hazard. The acute cases of fulminating poisoning by different pollutants are well established, but the effects of insidiously deposited environmental agents in the body in microgram doses need to be investigated. The systematic study of the relationship between the deposited environmental materials during life and the tissue alterations would be a challenging role for anatomic pathology. To achieve this task, it will be necessary to re-tool the 19th century autopsy room where microbiological agents were recognized as the primary health hazard, to a 20th century laboratory with instruments capable of exact quantitation, which recognizes the microchemical agents as a danger to health. The concept of Environmental Research Pathology is proposed in a programmatic outline form.

Diet has been found to significantly affect hexachlorobenzene (HCB) accumulation in 20-week old female Osborne Mendel rats. These animals were all fed mg/kg body weight HCB/day for 6, 12 and 18 days, high carbohydrate (67.7% w/w) or high fat (45.3% w/w) diets which were isocaloric with respect to protein. The effect of two sources of carbohydrate, cornstarch and sucrose, on the accumulation of HCB was studied in separate experiments. Feeding the high fat diet not only resulted in higher carcass fat content but also promoted HCB accumulation in the perirenal fat pad, gastrocnemius muscle and liver. these same tissues from obese animals fed the high fat diet had substantially higher fat levels than those fed high carbohydrate diets. Much less HCB was present in the feces of animals fed the high fat ration so the high fat diet presumably facilitated HCB absorption from the gastrointestinal tract. The differences in HCB accumulation in rats fed diets with different carbohydrate sources were slight, but the sucrose diet promoted greater HCB accumulation than the cornstarch diet.

Pregnant F2 dihybrid mice received either a vehicle-control or 1 of 2 doses of the anticholinesterase pesticides Carbofuran (0.01 or 0.50 mg/kg) or Diazinon (0.18 or 9.00 mg/kg) in the diet daily throughout gestation. All mothers gave birth to viable, overtly normal offspring at term. However, a significant number (12%) of pups born to dams who received 9.00 mg/kg Diazinon died prior to weaning on day 28; necropsy findings were consistent with death from respiratory infection. There was no significant difference in mortality between control and pesticide-exposed offspring once they reached 28 days of age. Determinations of 5 different classes of serum immunoglobulin (Ig) concentrations (IgG1,IgG2a,IgG2b, IgA, IgM) at 101, 400 and 800 days of age indicated transient but consistent disturbances of 2 Ig classes in offspring as a result of prenatal pesticide exposure. IgG1 concentrations of male offspring exposed to 0.50 mg/kg Carbofuran or 0.18 mg/kg Diazinon were significantly elevated at 101 days but not at 400 or 800 days of age. IgG1 concentrations of female offspring exposed to 0.01 mg/kg Carbofuran or 9.00 mg/kg Diazinon were significantly depressed at 101 days but not different from controls at 400 or 800 days of age. Changes in IgG2b levels generally were similar to those recorded for IgG1 but of smaller magnitude. There were no significant effects on serum IgG2b or IgM concentrations, and only equivocal effects on IgA, as a consequence of prenatal exposure to either pesticide.

We have investigated a short-term initiation/promotion assay in rat liver for chemical carcinogens. Diethylnitrosamine was used as the initiator and phenobarbital and partial hepatectomy as promoters. Initiation was determined as the focal induction of gamma-glutamyl transpeptidase activity. The protocol of the assay consisted of the following: (1) the initiator was administered, (2) one week later the rats were given 500 ppm phenobarbital in their drinking water (3) one week later 2/3 partial hepatectomy was performed and (4) the rats were maintained on 100 ppm phenobarbital for an additional four weeks. The assay was sensitive to 0.003 mmole/kg diethylnitrosamine and the number of gamma-glutamyl transpeptidase positive islands increased as a function of diethylnitrosamine dose up to at least 2 mmole/kg. Multiple doses containing a low level of diethylnitrosamine were additive. It is proposed that the assay can be used to detect initiators and promoters.

The spontaneous hepatocellular neoplasms of C3H (MTV-ve) male mice were compared with the hepatic tumors induced in these animals by diethylnitrosamine (DEN) and dieldrin. No morphologic differences could be detected by light or electron microscopy between the spontaneous and induced lesions. However, the animals given diethylnitrosamine or dieldrin developed the lesions earlier, in greater numbers and of larger size. The earliest change was the development of foci composed of clear cells. Later nodules appeared which were composed of clear or basophilic cells. These lesions were followed by and presumably progressed to nodules of trabecular hepatocellular carcinomas. It is postulated that in this series, the first morphological step in the neoplastic transformation is the appearance of unusually clear hepatocytes. Ultrastructurally, the clear cells had increased glycogen and lipid droplets and a decrease in smooth endoplasmic reticulum. The basophilic cells seen later resembled the clear cells except for having a greatly increased rough endoplasmic reticulum. Trabecular hepatocellular carcinomas differed from benign nodules in the greater secretory activity of the rough endoplasmic reticulum, in the development of basement membranes at the vascular pole and of microvilli along the lateral cell membranes. The stepwise progression of normal hepatocytes to hepatocellular carcinoma is discussed on the basis of these sequential light microscopic and ultrastructural observations.