摘要:

Since ambient concentrations of ozone and nitrogen dioxide increase drug‐induced sleeping time in female mice, potential mechanisms were sought by investigating the effects of these gases on hepatic microsomal mixed‐function oxidases in female CD‐1 mice. A 3‐h exposure to 9800 μg O3/m3(5 ppm) or 9400 μg NO2/m3(5 ppm) did not change the concentration of cytochrome P‐450 significantly. Aniline hydroxylase, but not aminopyrine N‐demethylase or p‐nitroanisole O‐demethylase, activities were increased following a 3‐h exposure to 9400 μg O3/m3(5 ppm). Aniline hydroxylase activity was also increased after a 2‐d (5 h/d) exposure to 1960 μg O3/m3(1 ppm). None of these enzyme activities were affected by a 3‐h exposure to 9400 μg NO2/m3(5 ppm). In these studies, O3sometimes increased wet liver weight, and thus additional experiments were conducted. A 5‐h exposure to 1960 μg O3/m3(1 ppm) caused a lesser decrease in body weight than the decrease observed after a similar air exposure. Liver wet weights were elevated after O3exposure. However, there were no significant changes in liver dry weight, liver dry‐to‐wet‐weight ratio, or ratios of liver (wet or dry) weight to body weight. From these data, it is concluded that mechanisms other than those investigated are responsible for the effect of O3and NO2on drug‐induced sleeping time. However, the activity of one mixed‐function oxidase was slightly increased by O3, indicating a hitherto unrecognized systemic effect of O3exposure.

ISSN:0098-4108    

DOI:10.1080/15287398209530207

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The biochemical effects of a 5‐d continuous exposure to 0.45 ppm (882 μg/m3) O3were studied in the lungs of 2‐mo‐old male, specific‐pathogen‐free mice (Swiss Webster) and three strains of rats (Long‐Evans, Wistar, and Sprague‐Dawley). The results, expressed per lung, indicated a general increase in lung weight, DNA and protein contents, oxygen consumption, sulfhydryl metabolism, and the activities of several NADP+‐reducing enzymes for all exposed animals relative to their controls. When the increases in the two species (mice versus three strains of rats) were compared, the mice showed significantly higher increases than the rats in several parameters. The responses among the three strains of rats were variable, but the differences were not significant. These observations suggest that Swiss Webster mice may offer a more sensitive animal model than rats for studying the pulmonary effects of a given low‐level O3exposure.

ISSN:0098-4108    

DOI:10.1080/15287398209530208

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

An ip LDSO value (68 mg/kg) for folpet, a widely used fungicide, was determined using adult male Sprague‐Dawley rats. Next, the compound in sublethal doses was given to the animals orally as well as intraperitoneally (ip), and its effects on the levels of hepatic drug‐metabolizing enzymes and serum glutamic oxalacetic transaminase (SGOT) were compared. An ip dose as small as 50 mg/kg was able to significantly alter the levels of these enzymes reflecting on liver damage, while an oral dose up to 10 times the ip dose did not have an appreciable effect on the enzymes and did not cause any visible toxic symptoms in the animals. In vitro incubation of folpet with rat liver microsomes with and without an NADPH‐generating system showed that the fungicide may not require metabolism to exert inhibitory effect on the microsomal enzymes. In fact, the data suggest that the parent compound or its nonenzymatic degradation product(s) caused destruction of microsomal cytochrome P‐450 in vitro. However, this loss of the hemoprotein by folpet could be prevented by prior addition of reduced glutathione in the incubation media.

ISSN:0098-4108    

DOI:10.1080/15287398209530209

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

A polybromlnated biphenyl (PBB) mixture was fractionated by normal‐phase preparative high‐performance liquid chromatography. The hexane fractions were concentrated and applied to rabbit ears. Only the most polar fraction produced hyperkeratosis on the rabbit ears. This active fraction was subfractionated by using the same procedure. Again, the extent of hyperkeratotic activity increased with increasing polarity. The PBBs of the largest concentration levels in the active fraction were purified by preparative gas chromatography and tested on rabbit ears. The major compounds did not demonstrate hyperkeratotic activity.

ISSN:0098-4108    

DOI:10.1080/15287398209530210

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The metabolism and distribution of 2,4‐dichlorophenol (2,4‐DCP) were studied in the rat after intravenous administration of 10 mg/kg. 2,4‐DCP was determined by gas chromatography with an electron‐capture detector. The highest concentration of 2,4‐DCP was found in kidney, followed by liver, fat, and brain. 2,4‐DCP is metabolized to glucurondie and other conjugates. The parent compound and its conjugates were rapidly eliminated from the body. The half‐lives of 2,4‐DCP and its conjugates in plasma, fat, brain, liver, and kidney ranged from 4 to 30 min. The volume of distribution of 2,4‐DCP in plasma was 3.7 1/kg. Tissue/plasma ratios indicated that 2,4‐DCP has a greater affinity for kidney.

ISSN:0098-4108    

DOI:10.1080/15287398209530211

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Groups of 28 male and 28 female CD‐1 mice and Fischer 344 rats were exposed to a mixture of 1,3‐Dichloropropene and 1,2‐Dichloropropane (D‐D) vapors. Exposure concentrations were 0, 5 (4.7), 15 (14.4), or 50 (53.7) ppm, 6 h/d, 5 d/wk for 6 or 12 wk. The following parameters were evaluated: pharmacotoxic signs, body weights, hematology (HGB, HCT, RBC, WBC, and diff. leukocyte count), serum chemistry (BUN, GLU, ALB, GPT, and ALP), urinalysis, gross pathology, histopathology, organ weights, and organ weight/body weight ratios of brain, heart, liver, kidneys, testes or ovaries, and adrenals. The only exposure‐related clinical effects observed were increased mean liver/body weight ratios of male rats and mean kidney/body weight ratios of female rats at the 50 ppm exposure level. Slight to moderate diffuse hepatocytic enlargement in 12 of 21 of the 50‐ppm male mice after 12 wk exposure was the only compound‐related histopathologic change present.

ISSN:0098-4108    

DOI:10.1080/15287398209530212

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The absorption, distribution, and excretion of a highly chlorinated dicarboxylic acid, chlorendic acid, was studied in the male Fischer 344 rat. [14C] Chlorendic acid was absorbed after on oral dose of 7. 7 μmol per kilogram of body weight. The distribution in various tissues was similar whether the treatment was by the oral or the intravenous route. The major site of [14C]chlorendic acid deposition was the liver, with smaller amounts found in the blood, muscle, skin, and kidneys. Chlorendic acid‐derived radioactivity was excreted primarily through the bile and into the feces. The urine contained less than 6% of the total dose. Within 1 d, more than 75% of the total dose was excreted in the feces, primarily as metabolites. Radioactivity in the liver was also primarily metabolites of chlorendic acid. Thus, chlorendic acid was absorbed, metabolized, and excreted primarily in the feces as metabolites. The rapid metabolism and biliary excretion of chlorendic acid contrast with observations for the closely related lipophilic compounds aldrin and dieldrin.

ISSN:0098-4108    

DOI:10.1080/15287398209530213

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The effects of tobacco smoke extracts on collagen and total protein synthesis by fibro‐blast cell cultures were studied. Tobacco extract with a nicotine concentration of 35 nmol per milliliter of culture medium increased collagen production but not protein secretion in the culture medium. Not only the rate of collagen synthesis but also the types of collagen produced were affected; in particular, there was a decrease of type III collagen.

ISSN:0098-4108    

DOI:10.1080/15287398209530214

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The comparative effects of the antioxidants, butylated hydroxyanisole (BHA), ethoxyquin, and cysteine on pyrrolizidine‐alkaloid‐induced (PA‐induced) lethality and acute hepatotoxicity were assessed in female mice. Diets containing 0.75% BHA, 0.25% ethoxyquin, or 1% cysteine were fed to mice for 10 d before the ip administration of mixed PAs from Senecio jacobaea (tansy ragwort), 280 mg/kg. Without the dietary antioxidants, the PAs produced 100% mortality in 24 h. The BHA and ethoxyquin diets were completely and partially protective, respectively, against the PA‐induced lethality. The deaths were associated with severe hemorrhagic lesions in liver with or without hepatocytic necrosis. Both BHA and ethoxyquin significantly reduced the incidence of the hemorrhagic lesions but not the necrotic lesions in liver. Cysteine had no significant effect on either mortality or the liver lesions induced by the mixed PAs. These results suggest that dietary antioxidants have differential protective effects against lethality and acute hepatotoxicity induced by mixed PAs from tansy ragwort.

ISSN:0098-4108    

DOI:10.1080/15287398209530215

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Auramine O has been reported to be carcinogenic in rats and mice. It has been reported as positive in some mutagenicity studies and negative in others. We have found that commercial auramine O is positive in inducing DNA damage in vivo in liver, kidney, and bone marrow cells. DNA damage was also induced after treatment in vitro of a human cell line. Commercial auramine O was also clearly positive for sister chromatid exchange (SCE) induction in vivo in bone marrow cells. Purified auramine was negative in terms of DNA damage and SCE induction. Our commercial auramine O had Michler's ketone as a major contaminant. This compound was capable of inducing both DNA fragmentation and an increase of SCE.

ISSN:0098-4108    

DOI:10.1080/15287398209530216

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor