摘要:

Paraquat (PQ) has specific pneumotoxicity in humans. Its effects on phospholipid metabolism in type 2 pneumocytes, A‐549, and in lung fibroblasts, WI‐38, were examined. PQ inhibited the incorporation of palmitic acid into phosphatidyl‐ethanolamine by 42%, but did not inhibit the incorporation Into phosphatidyichoiine. PQ also inhibited the incorporation of acetate into phosphatidyichoiine and ethanol‐amine by 82–88% in A‐549 cells and by 92% in WI‐38 cells. PQ inhibited the incorporation of choline into phosphatidyichoiine and ethanolamine by 55 and 73%, respectively. Phosphatidyichoiine was detected in the medium of A‐549 cells. PQ completely inhibited this phosphatidyichoiine secretion. These results suggest that PQ has inhibitory effects on phospholipid synthesis and excretion in human type 2 pneumocytes.

ISSN:0098-4108    

DOI:10.1080/15287398209530185

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The neurotoxic insecticide chlordecone was administered orally to “young” (4–6 wk old) and “old” (6 mo old) mice in a dose of 25 mg/kg·d in 10 ml/kg corn oil. Age‐matched control mice received 10 ml/kg·d corn oil. The acute (24 h after a single dose) and subchronic (24 h after 8 daily doses) effects of chlordecone on content and subcellular distribution of Ca in the brain were studied. Significant differences in Ca content and subcellular distribution were found between the young and old control mice. Whole brains of old mice had significantly greater amounts of total brain Ca, protein‐bound Ca, and mitochondrial Ca than did those of young mice, but significantly less nuclear and cytosol Ca. Acute exposure to chlordecone (no signs of neurotoxicity) increased significantly total brain, protein‐bound, nuclear, mitochondrial, and myelin Ca in brains from young mice. However, under the same chlordecone exposure conditions, old mice had significantly decreased total brain, protein‐bound, and mitochondrial Ca with significantly increased nuclear Ca content. It is suggested that aging caused altered biochemical responses to the neurotoxic agent, at least at subtoxic doses or exposure times. When young mice received chlordecone for 8 d and were suffering severe chlordecone‐induced tremors at the times of sacrifice, their brains were found to have significantly decreased total, protein‐bound, myelin, and synaptosomal Ca. Nuclear Ca was increased. The increased excitation of the central nervous system evidenced as severe tremors induced by chlordecone might be due, at least in part, to chlordecone‐induced Ca deficiency in brain synaptosomes. Such Ca deficiency may decrease the Ca‐dependent release of the CNS inhibitory transmitters γ‐aminobutyric acid (GABA) and dopamine.

ISSN:0098-4108    

DOI:10.1080/15287398209530186

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The single‐dose and repeated‐exposure toxicity of a synthetic mixture of 30 nitro‐toluene analogs, representative of a complex industrial wastewater termed condensate water, was evaluated in dogs, rats, and mice. The single‐dose oral LDSOs for the synthetic condensate water (CW) were 447 and 295 mg/kg in male and female rats, respectively. In the repeated‐exposure studies, dogs were given 0, 0.05, 0.5, or 5 mg of CW per kilogram of body weight by capsule daily for 26 wk. Rats and mice received 0, 0.001, 0.01, or 0.1% of this mixture in their diet for 4 or 13 wk. Groups of each rodent species were set aside for 4 wk to assess recovery. The most notable findings were a compensatory anemia with reticulocytosis (severe in rats), Heinz body formation, and related blood cell abnormalities and hemosiderin in the spleen; pigmentation in the liver cells; atrophy and aspermia in the testes; hyperplasia and inflammation in the female reproductive organs; and neurotoxic signs at the high doses. Rats and mice also experienced food intake and body weight depression and exhibited some alterations in organ weights (spleen, testes, and liver). The findings were referable principally to the two major components 2,4,‐ and 2,6‐dinitrotoluene, but the “no observable effects” levels were lower for the mixture.

ISSN:0098-4108    

DOI:10.1080/15287398209530187

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The short‐term oral toxicity of 2,4,6‐trinitrotoluene (α‐TNT) was determined in dogs, rats, and mice. Single‐dose oral LD50s for α‐TNT in corn oil were 1320 and 794 mg/kg in male and female rats, respectively, and 660 mg/kg in both male and female mice. For multiple‐dose studies, dogs were dosed daily for up to 13 wk with α‐TNT at 0, 0.2, 2.0, or 20 mg/kg by capsule; rats received 0, 0.002, 0.01, 0.05, or 0.25% and mice received 0, 0.001, 0.005, 0.025, or 0.125% α‐TNT in their diets over the same period. All species receiving the highest doses exhibited anemia, with reduced erythrocytes, hemoglobin, and hematocrit. Alterations were observed in organ weights, including enlarged spleens (accompanied by hemosiderosis) and livers, and depressed body weight and/or body weight gain (temporary in dogs and mice). Alterations in clinical chemistry values included elevated cholesterol and depressed serum glutamic‐pyruvic transaminase activity in dogs and rats; no effect on serum glutamic‐oxaloacetic transaminase activity was observed. Some effects, such as SGPT depression in rats, appeared after 13 wk, suggesting a cumulative toxicity. Reduced testes size was observed in rats at the highest dose regardless of length of exposure. Most of the toxic effects were reversible, but testicular atrophy was not in rats allowed a 4‐wk recovery period after treatment. Signs of anemia were present at intermediate dose levels. “No observable effects” levels for α‐TNT were: dogs, 0.20; rats, 1.42; and mice, 7.76 mg/kg·d.

ISSN:0098-4108    

DOI:10.1080/15287398209530188

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The oral toxicity of a mixture of 2,4,6‐trinitrotoluene and hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (1:0.62, w/w) compounds typically found in munitions plant effluents, was evaluated in mammalian species. Single‐dose oral LDSOs of the mixture were 574 and 594 mg/kg in male and female rats and 94 7 and 1130 mg/kg in male and female mice, respectively. Long dispersion periods during preparation or ultraviolet irradiation of the mixture lowered the LDSOs. In repeated‐exposure studies, dogs were given 0.50, 5.0 or 50 mg/kg‐d by capsule for up to 90 d. Rats and mice were fed the mixture in the diet at 0.005, 0.05, or 0.5% for 90 d; mice were also fed at 0.25%. Mortality resulted at the highest dose level in each species. All three species showed depression of body weight or body weight gain, depressed food intake, moderate to severe anemia, and alterations in the spleen (hemosiderosis), liver (hepatomegaly), and testes (atrophy) at the highest dose levels. Cholesterol was elevated in rats and dogs after 90 d. Several species differences were also noted. Uric acid values were elevated in rats but not in dogs, serum glutamic‐pyruvic transaminase (SGPT) activity was low in dogs but unchanged in rats, and rats developed hypoplasia of the uterus but dogs did not. Signs of anemia were present at the intermediate dose levels. The lowest dose level in all three species was designated at a “no observable effects” level, based on the absence of clearly treatment‐related effects. In a 4‐wk study, the irradiated mixture fed to rats at 0.003, 0.03, or 0.3% in the diet was less toxic than the unirradiated mixture.

ISSN:0098-4108    

DOI:10.1080/15287398209530189

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Addition of mineral oil to the diet (5%) of two rhesus monkeys that were dosed 29 wk earlier with 2,4,5,2′,4′,5′‐hexabromobiphenyl (HBB) produced a 175% increase in fecal excretion of HBB. A third rhesus monkey was provided with a complete biliary bypass, which permitted the reintroduction of the monkey's own bile or the introduction of the same amount of exogenous bile, which was obtained from control donor monkeys. This experimental design made it possible to measure the portion of fecal excretion that was due to biliary elimination and the portion that was due to intestinal elimination. The effect of mineral oil and/or cholestyramine (CSA) on biliary and intestinal elimination of HBB in the rhesus monkey was then investigated. The results show that (1) fecal excretion of HBB and/or metabolites is due to both biliary and intestinal elimination; (2) during the first 2 wk after completion of dosing, mineral oil does not influence fecal excretion of HBB significantly; (3) 6–7 wk after completion of dosing, mineral oil enhances fecal excretion of HBB by 5096; (4) 8 wk after the last dose of HBB, 4% CSA in the diet increases fecal excretion of HBB and/or metabolites by about 50% (5) mineral oil specifically stimulates Intestinal elimination of HBB; and (6) combined administration of mineral oil and CSA results in an additive effect.

ISSN:0098-4108    

DOI:10.1080/15287398209530190

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Adult, male Fischer 344 rats were treated singly or repeatedly with one of several doses of HgCI2(5, 10, or 20 mg/kg, poj or biphenyl (250, 500, or 1000 mg/kg, po). Urinalyses were conducted at various times after a single treatment or during repeated treatments. Groups of animals treated in the same manner were killed and the kidneys examined for histopathologic alterations.

ISSN:0098-4108    

DOI:10.1080/15287398209530191

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The insecticides toxaphene and carbaryl, when fed in the diet alone for 20 wk, were not tumorigenic to female All mice. Dietary levels of these insecticides were investigated for their effects on the incidence of lung tumors induced by oral administration of benzo[a]pyrene (BP). A significant reduction in BP‐induced lung tumors was found after feeding 100 ppm toxaphene for 12 wk or 200 ppm for 20 wk. In contrast, 1000 ppm carbaryl fed for 20 wk caused a significant enhancement of BP‐induced lung tumors. Mice that received toxaphene in the diet alone, or toxaphene and BP, showed an increase in BP hydroxylase activity in the liver and a decrease in enzyme activity in the lung. Carbaryl and BP increased BP hydroxylase activity in the lung without altering enzyme activity in the liver. Inhibition of lung BP hydroxylase activity was paralleled by a reduction in BP‐induced lung tumors in mice fed toxaphene. Conversely, increased lung BP hydroxylase activity was associated with an enhancement of BP‐induced lung tumors in animals fed carbaryl. The metabolism of BP by organs susceptible to BP‐induced tumors and possible mechanisms for interactions with the insecticides are discussed.

ISSN:0098-4108    

DOI:10.1080/15287398209530192

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Recent work has shown that V accumulates in the kidney and is a potent inhibitor of Na+, K+‐adenosinetriphosphatase (ATPase) in vitro. Thus, as a nutritionally required element, V may regulate cation transport. The effect of chronic intake of the metal on Na+, K+‐A TPase in vivo has not been reported. In this study laying strain chickens were fed calcium orthovanadate for 15 mo from d 1 of age at levels of 0, 25, 50, and 100 ppm in the diet. Whole tissue homogenates and 13,000 × g fractions were analyzed for A TPase activities. Concentrations of V producing 50% inhibition of Na+, K+‐ATPase activity ranged from 1.0 × 10−5M In liver to 1.8 × 10−6M in kidney, which was the most sensitive tissue tested in vitro. Mg2+‐A TPase was more resistant to V than Na+, K+‐A TPase. Studies in vivo suggested a V‐dependent inhibition of renal Na+, K+‐ATPase. Correlation of enzyme specific activity and levels of V in kidneys suggested V‐A TPase mediated alteration in renal function.

ISSN:0098-4108    

DOI:10.1080/15287398209530193

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The intraceliular fate of particulate crystalline αNiS, an inducer of neoplastic transformation which is readily phagocytized by cultured cells, was compared with that of particulate amorphous NiS, which does not have these properties. Amorphous and crystalline NiS both dissolve slowly in complete medium; phagocytized αNiS particles remain in the cytoplasm, where they dissolve more rapidly than extracellular particles. Thus the selective phagocytosis of aNiS accounts for both high intraceliular particle accumulation and high levels of soluble Ni relative to the surrounding medium. Since phagocytized aNiS particles do not enter the nucleus, dissolution in the cytoplasm may represent an activation step in carcinogenesis, forming soluble Ni which diffuses into the nucleus. Dissolution products from phagocytized aNiS were detected in subcellular fractions isolated from treated cells; the highest levels were found in the nuclei, mitochondria, and lysosomes. That the Ni in the subcellular fractions was dissolved is suggested by the fact that dissolution products from phagocytized aNiS were detected in, nuclei after centrifugation on sucrose pads, which substantially reduced contamination from cytoplasmic aNiS particles. Cytoplasmic dissolution of aNiS was enhanced by prior exposure of cells to the same compound. Loss of visible particles from cells was compared with loss of total Ni by use of α63NiS particles; the particles disappeared from almost half the cells during the first 2 d of treatment, while the total radioactivity associated with the cells and the total number of cells in the monolayer remained the same. The accelerated dissolution of aNiS after exposure to the same particles may be due to enhancement of lysosomal enzyme activity by particle phagocytosis. A 20–30% increase in intraceliular acid phosphatase activity was observed after treatment with crystalline, but not amorphous, NiS, suggesting enhanced lysosomal activity.

ISSN:0098-4108    

DOI:10.1080/15287398209530194

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor