摘要:

The in vitro effects of Cd, Zn, and Pb on pulmonary, adrenal, and hepatic microsomal enzyme activities in guinea pigs were compared. Cd and Zn produced concentration‐dependent (20–200 μM) decreases in benzphetamine demethylase and biphenyl hydroxylase activities in adrenal, liver, and lung. Pb had no significant effect on either enzyme in any of the tissues studied. Adrenal and pulmonary enzymes were more sensitive to the effects of Cd and Zn than were hepatic enzymes. Benzojalpyrene hydroxylase and ethoxycoumarin deethylase activities were decreased by Zn, Cd, and Pb in adrenal, liver, and lung microsomes. The inhibitory effects on benzol2]pyrene and ethoxycoumarin metabolism were far greater than those on benzphetamine or biphenyl metabolism. The relative potencies of the metals as inhibitors of xenobiotic metabolism were Zn > Cd > Pb. Cd and Zn also inhibited steroid 21‐hydroxylase activity in adrenal microsomes, but Pb had no effect on steroid metabolism. In addition, microsomal epoxide hydratase activity in adrenal, liver, and lung was inhibited by Cd but not by Zn or Pb. The results demonstrate that adrenal and pulmonary microsomal enzymes, like those in liver, are inhibited by various metals. Inhibition of mixed‐function oxidases by metals in vitro is apparently not related to changes in cytochrome P‐450 levels or substrate binding to cytochrome P‐450. In addition, the actions of Cd, Zn, and Pb in each tissue are highly dependent on the substrates employed.

ISSN:0098-4108    

DOI:10.1080/15287398109530125

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Absorption of Se from the nasal passages, lungs, gastrointestinal tract, and skin was studied in Fischer‐344 rats. Radiolabeled selenious acid and elemental Se particles were administered by inhalation, gavage, nasal instillation, and iv injection. Selenious acid was always absorbed into the general circulation more rapidly and to a greater extent than elemental Se. By 4 h after inhalation of selenious acid and elemental Se aerosols, 94% of the selenious acid and 57% of the elemental Se deposited in lungs was absorbed into blood. Of the selenious acid instilled into nasal passages, 18% was absorbed into blood; 16% of the elemental Se was absorbed. Gastrointestinal absorption was 87% for selenious acid and 50% for elemental Se. Selenious acid solutions were also painted onto the pelts of rats. From 10 to 30% of the selenious acid was absorbed through the skin. Following inhalation or injection of either Se compound, most of the Se was excreted in the urine. Significantly more Se appeared in feces of animals receiving elemental Se by gavage than animals receiving selenious acid. Results indicate that if people were to absorb inhaled Se from the upper respiratory tract in a manner similar to that of rats, one‐third more selenious acid would be absorbed into the general circulation than elemental Se. All Se deposited in the lungs would be absorbed into blood. However, selenious acid would be absorbed more rapidly than elemental Se.

ISSN:0098-4108    

DOI:10.1080/15287398109530126

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Mammalian sperm seems to provide an excellent cell type for monitoring mutagenic and other toxicological damage to the germinal tissue. Studies with mice indicated that most agents known for their mutagenic activity in vivo produced marked elevations in sperm abnormalities. To determine whether this response is typical of other species, groups of inbred Lakeview hamsters were exposed to ethyl methane‐sulfonate (EMS) and benzo[a]pyrene (BP) in five daily subacute ip doses ranging from 5 to 125 mg/kg and 2 to 50 my/kg, respectively. Percentage of abnormal sperm, testis weight, and body weight were monitored at wk 1, 4, and 10 after treatment. EMS exposures increased the frequency of sperm abnormalities and reduced sperm numbers and testis weights. Body weights were also affected. BP exposures did not induce sperm abnormalities; however, there were marked reductions in sperm number and testis weight. These findings are in agreement with results of EMS studies in the mouse; however, BP exposure did induce sperm abnormalities in the mouse.

ISSN:0098-4108    

DOI:10.1080/15287398109530127

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Induction of sister chromatid exchanges (SCEsj in cultures of Chinese hamster ovary cells by 10 anticholinesterase organophosphate insecticides was investigated. The insecticides were two phosphates (dichlorvos and dicrotophos), four sulfur‐containing organophosphates (malathion, parathion, leptophos, and diazinon), and four oxygen analogs of the latter (malaoxon, paraoxon, leptophosoxon, and diazoxonj. All of the compounds except diazinon induced statistically significant increases in SCE frequencies at concentrations between 0.03 and 1.0 mM. These results suggest that SCE induction is a common property of organophosphate insecticides. Compared to the sulfur‐containing organophosphates, the oxygen analogs consistently produced higher SCE frequencies and had stronger antiproliferative activity. Compared to two known genotoxicants, doxorubicin and ethyl methanesulfonate, the ability of organophosphates to produce SCEs is much weaker.

ISSN:0098-4108    

DOI:10.1080/15287398109530128

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

The distribution of some metals in nuclei and nucleoli of normal and regenerating rat liver was determined. The contents of Co, Zn, Cu, and Mn in nuclei were less than 3% of those in whole cells. Cr and Ni, which are known carcinogens, were present in cells in much smaller amounts than the metals above, but their contents in nuclei were more than 20% of those in cells. All of these metals were retained in nucleoli; the contents in nucleoli, per milligram of protein, were 3 (Zn) to 18 (Ni) times those in nuclei.

ISSN:0098-4108    

DOI:10.1080/15287398109530129

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

The mutagenicity of aliphatic (fraction J), one‐ to three‐ring aromatic (fraction 3), and four‐ to five‐ring aromatic (fraction 4) fractions of Prudhoe Bay crude oil and of a fuel oil no. 2 was investigated with a battery of in vitro mammalian and microbial assays. Chemical analysis of the fractions was carried out by gas capillary chromatog‐raphy‐mass spectrometry. In the Salmonella/mammfl//a/7 microsome test, both first fractions were negative, while fraction 3 of Prudhoe Bay crude and fraction 4 of both oils exhibited mutagenic activity with metabolic activation. In Chinese hamster ovary cells, all of the aromatic fractions, in the presence of metabolic activation, caused a significant increase in the number of sister chromatid exchanges. Chromosome aberrations were not caused by any of the aromatic fractions; however, fraction 3 of fuel oil no. 2 induced endoreduplication in the presence of metabolic activation.

ISSN:0098-4108    

DOI:10.1080/15287398109530130

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Delayed neurotoxicity after acute administration of organophosphates tohenscan be predicted by using the neurotoxic esterase (NTE) assay. The present study was designed to compare results obtained with the assay after single or multiple diisopropyl fluorophosphate (DFP) injections in hens. Adult White Leghorn hens were given DFP in a single (1.0 mg/kg) or in multiple (0.05 mg/kg‐d for 20 d) sc injections. Walking behavior was measured and both groups showed significant impairment by d 5 after the first or only DFP injection. However, impairmen t at the end of the study was greater in hens given a single injection of 1.0 mg/kg. All DFP‐treated hens exhibited axonal degeneration in brains, spinal cords, and peripheral nerves, and the changes in the two groups were of equal severity. Cervical and thoracic spinal cord lesions in hens given multiple DFP injections appeared to be primarily restricted to the myelinated spinocerebellar tracts. Inhibition of NTE was measured in brains, spinal cords, ilea, and thymuses 24 h after the single injection of 1.0 mg/kg DFP or after the 20th injection of 0.05 mg/kg DFP in additional hens. The NTE inhibition was significantly greater in all four tissues in the group given DFP as a single treatment. NTE in nerve andnonnerve tissues appeared to be differentially affected by single and multiple DFP treatments. Walking impairment and NTE inhibition were more marked when DFP was given in a single rather than 20 daily injections. However, in hens given multiple DFP injections the severity of central and peripheral nerve lesions was greater than was expected from the clinical and biochemical results.

ISSN:0098-4108    

DOI:10.1080/15287398109530131

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Cuticular and gastrointestinal penetration, in vivo metabolism, and excretion of [14C]acridine were investigated in the nymphal cricket Acheta domesticus (L.) to find a pharmacodynamic basis for this insect's differential susceptibility to acridine at different life stages. Topically applied [14C]acridine readily penetrated the cuticular exoskeleton of nymphs (half‐time of penetration, 48 min). Radiolabeled compounds appeared in the hemolymph within 0.5 h after ingestion of [14C]acridine and continued to move across the gut wall for 7.5 h. The biological half‐time was 18 h and the rate constant for elimination was 0.039 h−1after ingestion. Within 5 d after dosing, 97% of the dose was excreted. Several metabolites were present in the feces of nymphs fed [14C]acridine, and less than 13% of the extractable radioactivity was parent compound. The cuticle and the gastrointestinal tract proved to be ineffective barriers to acridine entry in A. domesticus. However, the ability to readily metabolize and excrete acridine probably contributes to the higher acridine tolerance observed in the nymphs and adults than in the eggs, which are susceptible to toxic effects.

ISSN:0098-4108    

DOI:10.1080/15287398109530132

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Experimental measurements of the growth of monodisperse dry NH4HSO4aerosols by H2O vapor condensation have been reported in the literature. These data are incorporated into an aerosol deposition model to study the behavior of inhaled NH4HSO4particles, which is of concern in relation to human health. The tracheobronchial tree is described by Weibel's model A morphology, and Landahl's formulas are used to compute particle deposition efficiencies. Enhanced losses in the trachea due to the action of the laryngeal jet are accounted for by using an empirical deposition efficiency equation. The effect of NH4HSO4aerosol growth is quantitated by comparisons of total and intrabronchial deposition probabilities with those of a nonhygroscopic aerosol of equal aerodynamic size. Computations indicate that hygroscopic growth effects are a function of the size of the particles inhaled. Total deposition efficiencies of NH4HSO4‐H2O droplet aerosols are greater than those of nonhygroscopic aerosols only if the former originate from dry NH4HSO4particles exceeding a critical geometric diameter of 0.3 μm. Growth effects are explained in terms of the relative efficiencies of the dominant deposition mechanisms active in the lung.

ISSN:0098-4108    

DOI:10.1080/15287398109530133

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

A semiautomated, microfluorometric assay has been developed for the detection of toxicant‐induced changes in lymphocyte DNA content at standard intervals after mitogen activation. DNA is quantitated by solubilizing the cells and determining the fluorescence enhancement that results from formation of the highly specific mithramycin: DNA adduct. The limit of detection is 0.2 μg (30,000 resting cell equivalents) per microtiter well. Correlation with the less sensitive, nonautomatable, diphenylamine DNA assay gives a correlation coefficient r = 0.97. Prototype substances representative of true immunotoxicants (prostaglandin E2) and common interfering substances (thymidine at < 5 × 10−4M) have been tested. The latter substance produces false positive results in the standard [3H] thymidine assay. The mithramycin assay does not inappropriately detect this interfering substance. It has the characteristics of a highly specific, accurate technique for screening and quantitating immunotoxic drugs, agents, and mediators in patient sera and other complex biological fluids.

ISSN:0098-4108    

DOI:10.1080/15287398109530134

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor