Journal of environmental pathology and toxicology最新文献

The incidence of spontaneous pheochromocytoma in rats varies with the strain, sex, age and diet of the animals. Treatment with growth hormone, estrogens, or radiation is associated with the occurrence of pheochromocytoma in the rat. Histological evidence and transplantation studies indicate that pheochromocytoma in rats possesses a low grade of malignancy. A transplantable radiation-induced pheochromocytoma model has been shown to be functionally active.

The in vitro metabolisms of dimethylnitrosamine (DMN) by liver slices and microsomal + soluble fractions, respectively, were studied in the rat, guinea pig, cat, duck, lizard and monkey using disappearance of DMN and the formation of formaldehyde, in situ, as indices of the decomposition of the compound. All the animal species investigated metabolised DMN, and the rate of metabolism of the compound was highest in media containing cat tissue and lowest in that containing duck tissue. The rat and guinea pig however appeared to metabolise DMN at comparable rates. Our results would suggest that DMN demethylase activity in the liver is a linear function of time. These results are discussed in relation to the toxicity of possible DMN metabolites.

Organophosphate pesticide residues have been responsible for periodic outbreaks of acute intoxication among California fieldworkers for over 30 years. In 1971, California established 're-entry intervals' to protect workers against overexposure to these residues. These intervals are stipulated times which must elapse between pesticide application and entry into the field for work involving substantial foliar or soil contact. The re-entry strategy depends upon a relatively predictable relation between time post-application and the level of the pesticide residue. It now appears that there are thiophosphates for which the residue hazard is not related to time in a stable way. This circumstance and the continued occurrence of poisoning incidents have focused attention on the quantitative aspects of the relationships between pesticide residue and toxicological response in humans. In the last decade, considerable progress has been made in elucidating these relationships and it now appears to be possible to outline the data requirements for a comprehensive regulatory solution to this longstanding occupational health problem.

Groups of male and female Fischer 344 rats were administered acrylamide in their drinking water at 0, 0.05, 0.2, 1, 5, or 20 mg/kg/day for up to 93 days. Following the administration of acrylamide in the drinking water, male rats from each dose level were held for up to 144 days of recovery. The 20 mg/kg/day groups had definite treatment-related effects after 92 (males) and 93 (females) days. They were dragging the rear limbs, body weights were decreased, serum cholinesterase activity was decreased in top dose females, and packed cell volume, red blood cell, and hemoglobin values were slightly decreased in males and females. In the 20 mg/kg/day groups, the primary target tissue was the peripheral nerve with lesions consisting of severe degeneration characterized by demyelinization and axonal loss. Slight spinal cord degeneration was observed. Other effects included atrophy of skeletal muscle, testicular atrophy, and distended urinary bladders; these were probably secondary to the nerve degeneration. After 144 days of recovery, the lesions had partially or completely reversed. Parameters affected at the 5 mg/kg/day dose level after 92 (males) and 93 (females) days consisted of peripheral nerve degeneration which were of a lesser degree of severity than those seen in the 20 mg/kg/day groups and appeared to have completely reversed after 111 days of recovery. In rats given 1 mg/kg/day, a minimal treatment-related effect was observed in males after 92 days, and this was limited to very slight nerve degeneration using electron microscopy (females were not examined by electron microscopy). This observed effect appeared to have reversed after 25 days of recovery. No treatment-related effects were seen in any of the parameters monitored in the rats given 0.05 or 0.2 mg/kg/day of acrylamide.

Specific-pathogen-free rats were exposed to 400 ppm sulfur dioxide daily for up to 7 weeks. At intervals during exposure, tracheas were removed and incubated in vitro in culture medium containing radioactive glycoprotein precursors. The most prominent histological changes due to SO2 were progressive hypertrophy and hyperplasia of the submucosal mucous glands accompanied by a flattening of the epithelium with eventual recovery. Uptake of radioactive precursors into a highly purified mucin fraction correlated with these histological changes in the submucosal mucous glands, increasing progressively up to 4 times that of control. Uptake of precursors into specific mucins purified by DEAE-Sephacel showed that uptake into the 0.2 and 0.3 M NaCl fractions was stimulated several fold by SO2, and uptake into more highly acidic fractions, which was nearly absent in the control, was also greatly increased. Two weeks following the last exposure of the tracheas to SO2, their morphological and mucus-secreting properties showed signs of returning to that of the control.

In order to detect potential toxic effects of substances, relatively high doses generally are administered to relatively small numbers of laboratory animals. It is impossible to estimate low levels of disease incidence with precision at low environmental dose levels even with large numbers of laboratory animals. However, upper limits on risk can be obtained for convex dose response curves by linear interpolation between the lowest experimental dose level and zero. A simple mathematical algorithm is provided for low dose risk assessment from dose response data and the performance of this procedure is evaluated for a variety of toxicological data, including but not limited to carcinogenesis. The low dose confidence limits resulting from linear interpolation are similar to those obtained from the Armitage-Doll multistage model.

Analyses for selected components in random samples of natural product diets for experimental rodents revealed significant variations in content of nutrients and contaminants in various lots of feed. Modification of the diet and contamination with any of several toxicants appreciably affected the responses of experimental animals to specific drugs or chemicals under test, which could cause biased interpretation of results. Therefore, continuous monitoring of laboratory animals' diets and maintenance of quality control are necessary. For example, low magnesium concentrations may affect the kidney; excessive calcium concentration may influence absorption and utilization of zinc; excesses of vitamins A and D are highly toxic; deficiency or excess of selenium affects biological systems; and poor protein quality may provide inadequate or imbalanced amino acids and thereby influence structure and function of animal systems in experimental studies. Important contaminants are the mycotoxins (particularly aflatoxin), heavy metals (lead, mercury, cadmium, arsenic), nitrates and nitrosamine (N-dimethylnitrosamine), chlorinated hydrocarbons, and polychlorinated biphenyls.

Pregnant 9 weeks old Sprague-Dawley rats were exposed to the smoke of different research cigarettes (C1-C7). The cigarettes were different in smoke nicotine, condensate and carbon monoxide. The animals were divided in groups inhaling different smoke concentrations, numbers of inhalations per day and time periods per pregnancy. Carbon monoxide and dioxide content in the inhalation chamber increased dependent on time and concentration of smoke inhalation. Both parameters were highest after inhalation of smoke from cigarette C2. The weight of the pregnant rats was reduced after inhalation of high concentrations of smoke from cigarette C1 and c2. Weight and length of fetuses were reduced dependent on number and duration of smoke inhalation. High concentrations of cigarette smoke, twice daily for 21 days were more effective than smoke inhalation in the second part of the pregnancy. Inhalation of cigarette smoke during the second half of the pregnancy was more effective than smoke inhalation in the first ten days of pregnancy. cigarette C1 reduced the length and weight of fetuses more than cigarette C2 when concentration and number of inhalations per day were the same. The vapor phase in both cigarettes was not as effective as the total smoke. Resorptions and stillbirths were independent of treatment. Malformations were diagnosed only in one fetus.

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.