bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary α1‐microglobulin as an indicator protein of renal tubular dysfunction caused by environmental cadmium exposure
Authors: Tohyama Chiharu , Kobayashi Etsuko , Saiko Hiroshi , Sugihara Naoko , Nakano Atsuhiro , Mitane Yuko 
Published: October 2006

AbstractAn epidemiologic investigation was carried out to clarify the significance of the urinary excretion of α1‐microglobulin (α1‐MG) in people aged 50 years and over living in a Cd‐polluted area in Japan. Approximately 80% of the population participated in the health examination. The urinary and serum levels and the relative clearance of α1‐MG to creatinine clearance were compared with various parameters (age, urinary β2‐microglobulin (β2‐MG), total protein, Cd, Cu and Zn, serum β2‐MG, creatinine and blood urea nitrogen and relative clearances of α1‐MG, β2‐MG, inorganic phosphate and uric acid). It was found that the urinary excretion of α1‐MG is closely associated with the urinary Cd and Cu and with the indices of renal dysfunction listed above. These results suggest that the urinary α1‐MG level masrkedly reflects a degree of proximal tubular dysfunction and that it may be useful as one of the screening measures for proximal tubular dysfuction caused by environmental Cd exposure.
Comparative inhalation hazards of aluminum and brass powders using bronchopulmonary lavage as an indicator of lung damage
Authors: Thomson S. M. , Burnett D. C. , Bergmann J. D. , Hixson C. J. 
Published: October 2006

AbstractBronchopulmonary lavage has been used as a rapid screening test for acute lung injury from many pneumotoxic chemicals. We demonstrated the efficacy of lavage fluid analysis for detection of acute pulmonary damage from inhaled metal dusts. Groups of male, Fischer 344 rats were exposed 4 h to one of five dosage levels of either brass (200, 100, 50, 10, 1 mg m−3) or aluminum (1000, 200, 100, 50, 10 mg m−3). At 24 h, 14 days and 3 months post‐exposure (PE), rats were evaluated for physiological and histological alterations to correlate with enzymatic and cytological profiles of lavage fluid. At 24 h PE, there were dose‐related increases in lactate dehydrogenase and protein in lavage fluid of the brass exposed rats, acute inflammatory response in terminal airways, increases in macrophages and neutrophils, and increased pulmonary resistance. All reactions were resolved by 14 days PE. In contrast, alumium powder produced no alteration in pulmonary function, but elicited persistent changes in enzymatic and cytological lavage fluid parameters with multifocal microgranlomas in lungs and hilar lymph nodes. Bronchopulmonary lavage analysis was useful as an indicator of inhalation hazards of brass and aluminum powders.
Acute toxicity of brass particles to Daphnia magna
Authors: Johnson Dennis W. , Haley Mark V. , Hart Gayle S. , Muse William T. , Landis Wayne G. 
Published: October 2006

AbstractThe aquatic toxicity of brass particles was examined. Acute, 48 hour bioassays were performed using the water flea, Daphnia magna. Tests were conducted with uniform suspensions of uncoated brass particles, brass particles coated with a Teflon solution, silica particles, and titanium dioxide particles. The Teflon coating solution and the supernatant of the brass suspension (after settling of the brass) also were tested. All tests were conducted according to guidelines set forth by the US Environmental Protection Agency and the Organization for Economic Cooperation and Development. Mean EC50 determinations of 20.0 μg l−1 and 23.6 μg l−1 were calculated for uncoated brass particles and coated brass particles, respectively. The silica, titanium dioxide, and Teflon each had an EC50> 1 g−1. Chemical fate studies demonstrated that the brass dissociated to its ionic components of copper and zinc quickly at pH 2.0. At pH 5.0 and 6.5, the dissociation occurred too slowly to account for the observed toxicity. The data suggested that the toxicity is due to filtration by the daphnids and subsequent ingestion. EC50 determinations for the brass particles are nearly identical with published EC50 values for copper salts.
Evaluation of the relationship between chemical and biological monitoring of low‐level lead poisoning
Authors: Wigfield Donald C. , Wright Sandra C. , Chakrabarti Chuni L. , Karwowska Regina 
Published: October 2006

AbstractBlood lead levels, together with δ‐aminolevulinic acid dehydratase activity determinations have been measured on rats dosed with up to 1000 ppm lead acetate in their drinking water for periods up to 5 weeks. Despite evidence of a compensation mechanism developing in the enzyme determinations, enzyme activity ratios, if properly chosen, still correlate reasonably well (r=0.87) with blood lead levels. Activity ratios using data on the shoulders of pH‐activity profiles (e.g. activity ratios of 6.4 and 7.2), however, give much less satisfactory correlations. These data provide a more stringent test of the chemical monitor–biological monitor correlation than has previously been possible.
Induction of aryl hydrocarbon hydroxylase in rat tissue following intratracheal instillation of diesel particulate extract and Benzo[a]pyrene
Authors: Chen K. C. 
Published: October 2006

AbstractThe potential for aryl hydrocarbon hydroxylate (AHH) induction by inhaled diesel particles was assessed by intratracheal administration. Benzo[a]pyrene, (B[a]P) a reference compound, or an extract of particles, dissolved in gelatin‐saline solution was administered to Fischer 344 rats at several dose levels. Twenty‐four hours after administration of B[a]P or diesel particulate extract, the AHH activity increased in a dose‐response manner in the lung, but not in liver. The maximum increase in the AHH activity in the lung was observed 12 h after intratracheal instillation of B[a]P (5 mg/kg), and the levels remained elevated for seven days. The AHH activity in the liver reached the maximum 24 h after the administration, and returned rapidly to control values. In contrast, intratracheal instillation of diesel particulate extract resulted in a significant increase of AHH activity in the lungs only after doses greater than 6 mg kg−1. The activity, however, declined rapidly and returned to control values within 75 h. The liver AHH activity in this instance, remained unchanged throughout the experimental period. These data indicate that in the lung, hydrocarbons extracted from diesel particles are weak enzyme inducers and exposure to these compounds by intratracheal administration did not result in AHH induction in the liver. The results suggest that doses higher than those normally expected from occupational exposures will be required to induce AHH activity in organs examined.
Significance of the dog as ‘second animal species’ in toxicity testing for establishing the lowest ‘no‐toxic‐effect level’
Authors: Appelman L. M. , Feron V. J. 
Published: October 2006

AbstractThe toxicity data of 66 compounds adequately tested in the rat (as ‘prime animal species’) and in the dog (as ‘second animal species’) were studied to find out for how many of these compounds the study in dogs led to a lower ‘no‐toxic‐effect level’ (NTEL) than that found in the rat. From a quantitative point of view such information would contribute to a better insight into the desirability of toxicity studies in dogs, because acceptable daily intakes and permissible exposure levels in man are generally based on the lowest NTEL.For 44% of the compounds the NTEL in the dog was lower than that in the rat. When rat NTEL was divided by the arbitrary factor of 10, the adjusted NTEL was lower than the dog NTEL for 86% of the compounds tested in sub‐chronic studies, and for 80% of the compounds tested in chronic studies. Whether it is justifiable to substitute such an adjusted NTEL for a study in dogs should be judged from compound to compound. It mainly depends on the size of the margin between the NTEL in the rat (as ‘prime animal species’) and the (expected) actual exposure level in humans, and also on the acceptability of loosing additional qualitative toxicological information. When this margin is large enough (e.g. 1000 or more), a study in dogs might be superfluous, despite the loss of qualitative data. Such an approach could lead to a reduction of the number of animals in toxicity testing and also to a reduction of the costs.
The distribution of arsenic and cobalt in patients with laryngeal carcinoma
Authors: Collecchi Paola , Esposito Mauro , Brera Silvio , Mora Enzo , Mazzucotelli Ambrogio , Oddone Massimo 
Published: October 2006

AbstractThe objective of this study was to evaluate tissue and plasma concentrations of arsenic and cobalt in an attempt to discove the role of these elements in the malignant process. Using neutron activation analysis, arsenic and cobalt levels were determined in plasma and in non‐malignant and malignant human tissue in 15 patients with laryngeal carcinoma. Arsenic and cobalt levels were about 60% higher in tumor than in adjacent non‐malignant tissue (P<0.001): arsenic 72.4±18.0 ng/g versus 43.1±9.4 in non‐malignant tissues, and cobalt 68.7±7.3 ng/g versus 39.6±7.0 in non‐malignant tissues. Mean plasma arsenic and cobalt levels were also significantly higher in patients with laryngeal carcinoma than in healthy control subjects.
The effect of topically applied n‐butylester of 2,4‐dichlorophenoxyacetic acid on the immune response in mice
Authors: Blakley Barry R. , Schiefer Bruno H. 
Published: October 2006

AbstractSix‐week‐old female CD‐1 mice were administered the n‐butylester of 2,4‐dichlorophenoxyacetic acid (2,4‐D). The 2,4‐D ester was applied dermally at dosages ranging from 0 to 500 mg/kg (2,4‐D content) in the acute studies and 0 to 300 mg/kg in the 3 week subacute studies. Following acute exposure, antibody production against sheep red blood cells was supressed at higher exposure levels. Evidence of clinical toxicity, myotonia and depression, and histopathological alterations in the central nervous system including perivascular edema and ganglial cell necrosis, was also seen in the mice. No alterations were observed in the T‐ and B‐lymphocyte proliferative responses induced by concanavalin A, a T‐lymphocyte mitogen, or Escherichia coli lipopolyaccharide, a B‐lymphocyte mitogen. Subacute 2,4‐D ester exposure which produced minimal clinical or pathological alterations, had no effect on antibody production, but did enhance the B‐ and T‐lymphocyte proliferative responses. The immunosuppressive effects of acute 2,4‐D ester exposure which were observed in this study, were unlikely a direct immunological alteration, but rather a secondary manifestation of the clinical syndrome. Since the subacute exposure levels may be more comparable to occupational or environmental exposure, it is unlikely that 2,4‐D esters will have any major immunotoxicological significance in agricultural communities.
The long‐term study in rodents for identifying carcinogens: Some controversies and suggestions for improvements
Authors: Feron Victor J. , Kroes Robert 
Published: October 2006

AbstractDespite increasing standardization and international harmonization of the long‐term carcinogenicity study in rodents there are still areas of controversy such as high‐dose selection, duration of the test period, combining or not combining the chronic toxicity and the carcinogenicity study, the use of historical control data, conditions for redundancy of the study, and significance of studies of restricted design. It is discussed that the ‘Maximum Tolerated Dose’, or doses above and below the ‘metabolic break‐point’ should be included. In general a test period of 24 months is adequate, but the protocol should be flexible enough to allow extension beyond 24 months. Major advantages of the combined chronic toxicity/carcinogenicity study are that the toxicity and carcinogenicity data are obtained with the same sample of the test compound using the same batch of animals kept on the same diet under the same environmental conditions. It is discussed that the use of historical control data will not lead to a final conclusion on carcinogenic or noncarcinogenic potential of a compound. A long‐term carcinogenicity study is considered redundant (a) when adequate (semi‐chronic) toxicity studies including reproduction and mutagenicity tests and pre‐screens for carcinogenicity, do not indicate mutagenic or carcinogenic activity, and (b) when there is a wide margin (e.g. 1000) between the ‘no‐observed‐adverse effect level’ and the (presumed) exposure level in humans. Studies of restricted design and conduct may clearly demonstrate carcinogenicity but also may easily lead to inconclusive results.
The effects of cadmium on succinate and NADH‐linked substrate oxidations in rat hepatic mitochondria
Authors: Cameron I. , McNamee P. M. , Markham A. , Morgan R. M. , Wood M. 
Published: October 2006

AbstractLow concentrations of cadmium (3.3–40 μM) inhibited State 3 NADH‐linked respiration in rat hepatic mitochondria, but failed to release oligomycin (1 μM) inhibited State 3 respiration, or to significantly change the State 4 rate. In the presence of succinate, (40 μM) cadmium inhibited State 3 respiration by 89%, while concentrations between 3.3 and (13.3 μM) stimulated State 4 respiration. Higher concentrations caused marked inhibition. In the presence of succinate, cadmium released oligomycin inhibited State 3 respiration. Cadmium (0.001–1.0 mM) did not stimulate mitochondrial ATPase activity or inhibit ferricyanide reduction, but stimulated NAD+ linked mitochondrial dehydrogenase activities and NADH oxidation. These results indicate that cadmium interacts with either the NADH dehydrogenase complex or other NADH‐dependent enzymes and solely by an uncompling action.
Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats
Authors: Appelman L. M. , Woutersen R. A. , Fcron V. J. , Hooftman Ria N. , Notten W. R. F. 
Published: October 2006

AbstractThe effects of exposure pattern on the toxicity of acetaldehyde vapour were investigated in 4‐week inhalation studies. Male rats were exposed to 500 or 150 and 110 ppm for 6 h per day/5 days per week. One group of animals was exposed without interruption, the exposure of a second group was interrupted for 1.5 h between the first and second 3‐h periods, the exposure of a third group was similarly interrupted and for six 5 min periods exposure was increased sixfold.Peak exposures of up to 3000 ppm superimposed on 500 ppm acetaldehyde caused irritation and excitation, and reduced body weight gain. No such effects occurred after interrupted or uninterrupted exposure to 500 ppm acetaldehyde without peak loads. A reduced phagocytotic index of lung macrophages was found in each of the groups exposed to 500 ppm acetaldehyde, the effect being most marked in the group with superimposed peaks of 3000 ppm. Degeneration of the nasal olfactory epithelium was observed in rats uninterruptedly exposed to 500 ppm acetaldehyde. Interruption of the exposure or interruption combined with peak exposure did not visibly influence this adverse effect on the nose. No compound‐related effects were seen in rats interruptedly or uninterruptedly exposed to 150 ppm acetaldehyde can be considered a ‘no‐toxic‐effect level’ in male rats exposed for 6 h/day, 5 days/week, during a 4‐week period.It was concluded that the interruption of daily exposure by 1.5 h exposure‐free period or by the superimposition of six times 5 min peak exposure periods did not appreciably influence the nasocytotoxic potency of acetaldehyde. Futhermore for inhalation toxicity testing of irritants such as acetaldehyde the use of variable exposure patterns does not seem to produce more relevant toxicity data than the use of uninterrupted daily exposure to a fixed concentration.
Toxic and genotoxic action of electric‐arc welding fumes on cultured mammalian cells
Authors: Baker R. S. U. , Arlauskas A. , Tandon R. K. , Crisp P. T. , Ellis J. 
Published: October 2006

AbstractWelding fumes generated by manual metal arc welding (MMAW) with an automatic welding machine were extracted with water and both the soluble and insoluble fractions were investigated for mitotic delay and for sister chromatid exchange (SCE) induction in cultured Chinese hamster Iung (Don) cells. Five flux‐coated electrodes of varying composition were chosen as representative of those available. In general, watersoluble and water‐insoluble fractions induced SCE in proportion to their chromium (VI) content, and any contribution from chromium(III), fluorides, nickel, manganese or other fume constituents was minor. However, mitotic delay could not be explained in terms of the chromium(VI) concentration alone. This indicated that other components of both the soluble and insoluble fractions of the fumes were capable of inducing mitotic delay. The activity of insoluble fume fractions, either in mitotic delay‐ or in SCE‐induction, was markedly less than than that of soluble fractions. This was presumably because of the lower, though still significant, bioavailability of ‘insoluble’ components of the fume particles.
Time development of distribution and toxicity following single toxic APAP doses in male BOM:NMRI mice
Authors: Skoglund L. A. , Ingebrigtsen K. , Nafstad I. , Jansen J. Høgset 
Published: October 2006

AbstractThe time development of the biodistribution and the hepatotoxicity following peroral administration of 14C‐acetaminophen (APAP 400 or 800 mg.kg−1; 1μCi) was characterized in a trial procedure using male Bom:NMRI mice. APAP (400 mg.kg−1) caused a transitory hepatic glutathione (GSH) depletion while APAP 800 mg.kg−1 maximally depleted hepatic GSH throughout the 12 h trial period. A lag time between the initial GSH depletion and the ensuing hepatic necrosis was seen. From 8 h post dosing a decrease of 14C‐APAP or its metabolites coincided with recovery of the hepatic GSH level and the regeneration of the hepatic cells caused by APAP 400 mg.kg−1. Hepatic glycogen depletion preceded centrilobular necrosis, and irrespective of APAP dose definite kidney damage was absent. Irrespective of APAP dose the biodistribution of 14C‐APAP or its metabolites was predominantly in organs associated with metabolism and excretion. After APAP (800 mg.kg−1) significant amounts of 14C‐APAP or its metabolites were present up to 24 h post dosing. The operative status of the hepatic GSH conjugative system has an important influence on the rate of elimination of toxic APAP doses. Hepatic cell necrosis with a possible effect on the circulation may play an important secondary role in the elimination of toxic APAP doses. Factors which may influence the status of the hepatic GSH conjugative system and toxicokinctics of perorally administered APAP doses are discussed.
Induction of superoxide dismutase isozymes in rabbit lung due to aniline exposure
Authors: Kakkar Poonam , Viswanathan P. N. 
Published: October 2006

AbstractSingle exposure of rabbits to aniline vapors caused induction of superoxide dismutase isozymes and activity as evidenced by the incorporation of radioactive amino acids and prosthetic group metals into enzymatic protein zones of electrophoreograms. Induced of a new cytosolic isozyme following aniline exposure was also evident. Xenobiotic stress indicated a close relation between free radical processes and lung biotransformation mechanisms.
Nephrotoxic effect of Tris(2,3‐dibromopropyl) phosphate on rat urinary metabolites: Assessment from 13C‐NMR spectra of urines and biochemical and histopathological examinations
Authors: Fukuoka Masamichi , Takahashi Terue , Tanaka Akira , Yamaha Tsutomu , Naito Katushi , Nakaji Yukio , Kobayashi Kazuo , Tobe Masuo 
Published: October 2006

AbstractRats received either single oral doses of 0, 25, 50, 100 and 200 mg/kg tris(2,3‐dibromopropyl)phosphate (Tris‐BP) or repeated doses of 50, 100 and 200 mg/kg/day Tris‐BP for 7 days. Urine was collected over a 24‐hr period and subjected to 13C‐NMR and biochemical examinations. Tris‐BP produced significant increases of urinary glucose and lactate. Urinary γ‐glutamyitransferase, lactate dehydrogenase and alkaline phosphatase levels were significantly elevated on the first 2 days of post‐treatment. Histopathologically, the kidney exhibited proximal tubular damage at a dose of 200 mg/kg. There was a good correlation among the histopathological, biochemical results, and the 13C‐NMR urinary metabolite fingerprints in the assessment of Tris‐BP‐induced renal damage. The abnormal patterns of metabolite excretion suggested that the lesions produced by Tris‐BP were caused by changes in the metabolic function of tubular epithelial cells. The urinary excretion of lactate, enzymes and inhibition of glucose reabsorption from the tubular lumina may be attributed to necrosis and desquamation of the tubular cell.
The effect of lead on chemical‐ and viral‐induced tumor production in mice
Authors: Blakley B. R. 
Published: October 2006

AbstractFemale Swiss mice were exposed to lead in the drinking water at concentrations ranging from 0 to 1000 ppm for 105 or 280 day periods of time. The effect of lead on urethan‐induced pulmonary adenoma formation was evaluated in the 105 day study. Urethan‐induced sleeping times observed following ip injection of urethan (1.5 mg/g) after 3 weeks of lead exposure were not altered by lead indicating that lead did not affect the rate of urethan elimination. Pulmonary adenoma formation was evaluated 84 days later. Lead exposure did not affect the number of tumors produced, nor did it alter the mean tumor diameter in the lead treatment groups. This suggests that the immunosuppressive activity of lead does not enhance urethan‐induced adenoma formation. In the 280 day study, the incidence of spontaneous murine lymphocytic leukemia was evaluated. Leukemia was observed in all treatment groups. Mortality was greater in the lead‐exposed mice. Mice exposed to 50 or 1000 ppm lead had 41.6% and 58.3% more deaths associated with the virus. The median survival time was also reduced in the lead‐exposed mice. It appears that the immunosuppressive effects of lead allow for increased expression of the murine lymphocytic leukemia virus.
A comparison of a sheep bioassay and a chemical assay used to estimate the toxicity of lupin stubbles infected with Phomopsis leptostromiformis
Authors: Hancock G. R. , Allen J. G. 
Published: October 2006

AbstractFifteen lupin stubble samples were tested for toxicity using a sheep bioassay and a chemical assay. A good association, in the functional form of a quadratic equation, existed between the results provided by the two assays. Only 16% of the variance of the chemical assay results was not associated with the sheep bioassay results.