bluuebunny/crossref_metadata_2025_split huggingface dataset:
A survey of genetic toxicology testing in industry, contract laboratories and government
Authors: McCarroll N. E. , Farrow M. G. , McCarthy K. L. , Scribner H. E. 
Published: October 2006

AbstractGenetic Toxicology Association members from governmental, contract and industrial laboratories were surveyed to determine the status of 28 recognized genetic toxicology assays in their laboratories. Compiled results of the 1982 questionnaire indicate that the Ames test, in vitro cytogenetics, in vitro sister chromatid exchange, unscheduled DNA synthesis, mutation in Chinese hamster ovary cells at the HGPRT locus, and in vivo bone marrow assays were the most frequently performed routine tests by the majority of laboratory affiliations. Investigation of the number of transformation assays performed indicated a high routine use. However, their use was largely confined to contract laboratories. Volume analysis of chemicals tested for 1982 indicated: (i) contract laboratories studied the largest number of compounds over the broadest spectrum of assays; (ii) industrial laboratories processed more compounds in the Ames test than any other laboratory group; and (iii) governmental laboratories ranked lowest in numbers of compounds evaluated both in‐house and/or subcontracted.
Pulmonary biochemical response to slate dust in rats
Authors: Khan M. Firoze , Ali Shahid , Singh Shivendra V. , Rahman Qamar , Viswanathan P. N. 
Published: October 2006

AbstractThe biochemical changes in rat lungs due to intratracheal instillation of 50 mg of slate dust have been studied up to 150 days of dust exposure. The remarkable feature of lung changes was the turnover of collagen in experimental animals after 90 days, reaching substantially higher values at 150 days. A concurrent increase in hexosamine and sialic acid contents was also observed. The phospholipid content in the whole lung tissue, as well as in the mitochondria, was generally higher in the dust‐treated rats, particularly at the later stages. The mitochondrial cytochrome c oxidase and glutamate dehydrogenase activities increased, whereas monoamine oxidase was marginally affected. Mitochondria from experimental animals appeared to be in a swollen state, particularly at 120 days of exposure. The above results suggest that slate dust exerts its toxic effects by causing alterations in the tissue make‐up as well as in the mitochondrial functioning of the lung.
The influence of chemical form of zinc on the effects of toxic intraruminal doses of zinc to sheep
Authors: Smith B. L. , Embling P. P. 
Published: October 2006

AbstractThe EDTA, sulphate and oxide compounds of zinc were administered to sheep as a single intraruminal dose (480, 240 or 120 mg Zn per kg body weight) or as thrice‐weekly doses (240 mg Zn per kg body weight per dose) for 4 weeks. In the single‐dose experiment, serum zinc concentrations rose most rapidly, were highest and fell most rapidly in those animals receiving zinc EDTA. In the sheep receiving the sulphate, serum zinc concentrations were high and stayed high for 2 or 3 days. Zinc oxide caused slight, but prolonged, elevation of serum zinc. High concentrations of zinc were present in urine after administration of zinc EDTA. In the multiple‐dose experiments, the sheep dosed with zinc sulphate showed progressively higher elevations of serum zinc (first dose, 5–10 μg Zn ml−1; day 13, 30–60 μg Zn ml−1) and six of the seven sheep so dosed died before the final dose. At post mortem examination, many of these had lesions of the upper gastrointestinal tract and showed evidence of haemolytic crises. Sheep dosed with zinc oxide also had progressively higher peak serum zinc concentrations. In contrast, the peak serum concentrations for the zinc EDTA‐dosed sheep declined as the experiment progressed. No deaths occurred in the sheep dosed with zinc oxide or EDTA. Major pancreatic injury occurred in sheep dosed with the sulphate or oxide, but was only mild in the sheep dosed with the zinc EDTA. Diarrhea was mild and transitory in the EDTA‐dosed sheep, but more severe and persistent in those dosed with the sulphate. Organ zinc concentrations were very high in the sheep dosed with zinc sulphate or oxide and, although less elevated, were still high in the sheep dosed with the zinc EDTA. Mean pancreatic zinc concentrations were highest, with kidney and liver having slightly lower concentrations, for all the zinc compounds administered.
Alterations of drug‐induced toxicity in the mouse lymphoma assay by a rat hepatic microsomal metabolizing system (S‐9)
Authors: Oldham James W. , Preston Robert F. , Paulson John D. , Pritchard J. Frederick 
Published: October 2006

AbstractLarge differences in induced cellular toxicity were observed in the presence or absence of a rat liver micro‐somal metabolizing system (S‐9) during drug testing in the mouse lymphoma assay. After studying the fate of three drugs in this test system, several mechanisms were demonstrated whereby S‐9 reduced cellular toxicity. For N‐(4‐hydroxyphenyl)retinamide (HPR), fenoctimine sulfate and methyl palmoxirate, the drug concentrations (EC50) in the presence of S‐9 were, respectively, 11.5, 14.3 and 4.1 times the concentrations required to achieve comparable levels of toxicity in the absence of S‐9. HPR was metabolized by the S‐9 and sequestered in the microsomal membranes. This was associated with a marked reduction in the cellular accumulation of the drug. The reduced toxicity of fenoctimine sulfate in the presence of S‐9 was associated with extensive biotransformation to polar metabolites. This was accompanied by a reduction of radioactivity associated with the cells from 5.7% to 0.4% of the administered drug. Methyl palmoxirate was rapidly converted to its acid, palmoxirate, by horse serum enzymes present in the treatment medium. This provides an example of metabolism by a test system component other than the S‐9 or lymphoma cells. The reduced toxicity of this drug in the presence of S‐9 was attributed to further metabolism of palmoxirate and a reduction of the proportion of total radioactivity associated with the cells from 3.1% to 0.4%. These results emphasize the need for pilot toxicity studies, especially when components of the test system are varied, to assess the effect of drug concentration on the toxic response. Moreover, the results illustrate that drug disposition studies may provide explanations for observed changes in drug‐induced toxicity.
Subacute and chronic action of acrylonitrile on adrenals and gastrointestinal tract: Biochemical, functional and ultrastructural studies in the rat
Authors: Szabo S. , Gallagher G. T. , Silver E. H. , Maull E. A. , Horner H. C. , Komanicky P. , Melby J. C. , McComb D. J. , Kovacs K. 
Published: October 2006

AbstractA single dose of acrylonitrile can produce fatal adrenal apoplexy within approximately 2 h. Our previous studies also indicate that multiple injections of the chemical cause acute hemorrhagic and occasional nonperforating duodenal ulcers. Other authors have reported increase in gut and lung neoplasia after chronic exposure. The present study was designed to elucidate the subacute and chronic actions of acrylonitrile on the adrenals, stomach and duodenum by correlating biochemical, functional and morphologic investigations, as well as to gain insight into the mechanisms of action of acrylonitrile. Rats were exposed to 0, 0.0001% (1 ppm), 0.002%, 0.01%, 0.05% or 0.2% acrylonitrile in drinking water, or to the same amount of the chemical given through daily gavage, for 7, 21 or 60 days. Acrylonitrile caused a time‐ and dose‐dependent decrease in plasma corticosterone levels; aldosterone was affected only by the ‘high’ dose and prolonged time of exposure. Young rats were more susceptible than adults to this action of acrylonitrile. The adrenal cortex, especially the zona fasciculata, was atrophic in rats that had ingested the nitrile through drinking water. At 0.05% and 0.2%, it also caused decreased food intake and body weight gain. The adrenals were enlarged with a hyperplastic zona fasciculata after daily doses of a bolus of acrylonitrile. Ingestion of the chemical did not interfere with compensatory enlargement of the adrenal gland following unilateral adrenalectomy. On the other hand, the ACTH‐induced elevation of corticosterone plasma concentration was significantly attenuated by acrylonitrile in drinking water. Electron microscopy of the adrenal glands revealed no consistent changes in the steroid‐producing cells. We thus postulate that accelerated turnover of circulating corticoids and/or interference with the secretion or action of ACTH may primarily be responsible for the decreased plasma levels of corticosterone and aldosterone in rats that ingest acrylonitrile. The mucosa in the stomach at the junction of the forestomach and glandular region of animals that had ingested acrylonitrile was hyperplastic. The corpus also showed regional mucosal hyperplasia with the appearance of ‘cobble‐stoning’. These changes were preceded and associated with an elevated concentration of non‐protein sulfhydryls mostly in the mucosa of the glandular stomach. A similar, less prominent elevation also occurred in the proximal duodenum. These alterations may resemble the preneoplastic combination of elevated glutathione and focal hyperplasia described in the liver with hepatocarcinogens. Acrylonitrile thus serves as a model chemical which affects the adrenal gland and gastrointestinal system.
Subacute oral toxicity of tri‐n‐butyl phosphate in the sprague–dawley rat
Authors: Laham S. , Long G. , Broxup B. 
Published: October 2006

AbstractTri‐n‐butyl phosphate was administered by gavage to male and female Sprague‐Dawley rats for 14 consecutive days (low dose: 0.14 ml kg−1; high dose: 0.42 ml kg−1). Effects of this chemical were investigated at the end of the feeding period. Histopathological examination of the testes (high‐dose group) showed the presence of microscopic degenerative changes in the seminiferous tubules. No other abnormal microscopic changes were observed.
Zinc, copper, manganese and iron in rat organs after the administration and withdrawal of aflatoxin B1
Authors: Ikegwuonu Fidelis I. 
Published: October 2006

AbstractThe in vivo levels of zinc, copper, manganese and iron were determined in the testis, kidney and three brain regions (cerebellum, cerebrum and medulla oblongata) from rats intrapertoneally injected with 20 μg per kg body weight of aflatoxin B1 for 6 weeks. Similar investigations were made after a recovery period of 6 weeks. The results obtained were compared with those of pair‐fed control rats. The aflatoxin B1‐induced decrease in testicular zinc was not reversed after the recovery of the rats. On the contrary, the significantly increased zinc concentration in the other organs following aflatoxin B1 exposure, reverted to the control level, as judged by significant levels. Only in the kidney was there accumulation of copper, even after the cessation of aflatoxin B1 administration. The marked increase in the manganese concentration of all the organs following repeated toxin administration, persisted only in the brain regions after the recovery. Aflatoxin B1 treatment significantly decreased the iron concentration in the testis, kidney, cerebellum and cerebrum. Recovery did not alter this trend. Iron concentration in the medulla oblongata was, however, not significantly changed in the presence of aflatoxin B1. The present data suggest that the repeated administration of aflatoxin B1 to rats could result in either a permanent or temporary re‐distribution of these elements in the organs examined.
Quantitative analysis of α, β‐thujone, pulegone, safrole, coumarin and β‐asarone in alcoholic beverages by selected‐ion monitoring
Authors: Galli Corrado L. , Galli Giovanni , Tragni Elena , Caruso Donatella , Fiecchi Alberto 
Published: October 2006

AbstractInterest in the quantitative analysis of flavouring agents in alcoholic beverages arises from the possible toxicological consequences deriving from their use. The method reported here, based on gas chromatography with selected‐ion monitoring mass spectrometry (SIM), allows the simultaneous measurement of α,β‐thujone, pulegone, safrole, coumarin and β‐asarone at the ppb level in alcoholic beverages.
Sub‐acute versus sub‐chronic oral toxicity study in rats: Comparative study of 82 compounds
Authors: Woutersen Rund A. , Til Heero P. , Feron Victor J. 
Published: October 2006

AbstractToxicity data of 82 compounds, tested in both a sub‐acute and a sub‐chronic study, were evaluated to find out whether it is possible to substitute a sub‐acute for a sub‐chronic study without losing quantitative information. The no‐effect level (NEL) and the minimal‐effect level (MEL) were used as the basis for comparison. For each of the compounds, the sub‐acute and sub‐chronic studies were performed under similar conditions, with the same strain of rats and with a comparable range of dietary levels. It appeared that the NEL in the sub‐acute study was equal to the NEL in the sub‐chronic study for 56% of the compounds. For 44% of the compounds reviewed, the NEL in the sub‐chronic test was lower than the NEL in the sub‐acute test, indicating that a sub‐chronic study cannot simply be replaced by a sub‐acute study. However, it may be acceptable to use the NEL obtained in a sub‐acute study as a basis for establishing acceptable daily intakes or permissible exposure levels for humans if an additional safety factor of 10 is applied. Furthermore, it was concluded that the conventional sub‐acute study, including some selected haematological and biochemical parameters, seems extremely useful to obtain quick and reliable information on the toxicity of the numerous non‐regulated chemicals which have to be investigated in the years to come.
Chronic toxicity of S‐(trans‐1,2‐dichlorovinyl)‐L‐cysteine in mice
Authors: Jaffe Deborah R. , Gandolfi A. Jay , Nagle Raymond B. 
Published: October 2006

AbstractS‐(trans‐1,2‐Dichlorovinyl)‐L‐cysteine (DCVC) exposure causes acute renal tubular cytotoxicity. To further characterize the effects of DCVC, a chronic study was undertaken. Male Swiss–Webster mice received DCVC dissolved in their drinking water at 0.01, 0.05 and 0.1 mg ml−1. At 4, 8, 21 and 37 weeks, animals were terminated. Bladders, spleens, livers, kidneys and eyes were removed for histopathological examination. At 0.05 and 0.1 mg ml−1 DCVC, growth retardation was evident by 21 weeks. By 26 weeks, all animals in the 0.1 mg ml−1 group had developed cortical cataracts. Cytomegaly, nuclear hyperchromatism and multiple nucleoli were noted in the cells of the pars recta region of the kidney by 4 weeks and correlated to time and dose. At later time points, renal tubular atrophy and early interstitial fibrosis were evident. The epithelial cytological cellular abnormalities appear to be dose‐related. Minor pathological changes were noted in the spleen, while there was no effect on the liver or bladder. Chronic ingestion of DCVC results in severe kidney injury.
The effects of fasting on the acute oral toxicity of nine chemicals in the rat
Authors: Dashiell O. L. , Kennedy Gerald L. 
Published: October 2006

AbstractNine chemicals, with a range from extremely to slightly toxic, were used to measure the oral LD50 in both fasted (24‐h) and non‐fasted rats. Each chemical was tested as a solution or suspension in corn oil, responses within 14 days post‐treatment were evaluated, and LD50s were calculated. Hexachlorophene was more toxic in non‐fasted rats. The LD50 values for tetraethyl lead, methomyl and hexamethylenediamine were essentially the same in both fasted and non‐fasted rats. Adiponitrile, bromobenzene, caffeine, carbon tetrachloride and N‐butyl‐1,6‐hexamediamine yielded lower LD50 values in fasted rats. The use of non‐fasted rats in acute oral toxicity determinations allows both the establishment of relative potency and the estimation of dosage levels for further repeated dose oral studies. The LD50 values obtained were generally (7 of 9) higher in non‐fasted rats, but the magnitude of the differences was not great enough to suggest routine use of both fasted and non‐fasted rats in oral toxicity studies.
Screening for ochratoxin A in blood by flow injection analysis
Authors: Hult Karl , Fuchs Radovan , Peraica Maja , Pleština Radovan , Čeović Stjepan 
Published: October 2006

AbstractA micromethod for ochratoxin A detection in human sera by flow injection technique is described. The method requires 50 μl of sera, and it is designed to distinguish samples containing less than 10 ng ochratoxin A per ml. The method is based on fluorescence measurement following a simple extraction procedure for which very small amounts of chemicals are needed. Since the method is not confirmatory, all samples showing fluorescence above a certain intensity have to be reanalysed with some other method where a confirmation step in included. Because of the small amount of serum needed and the rapid procedure (less than 15 min), a large number of samples can be analysed very quickly. The method may therefore be applicable for large screening campaigns conducted to determine the presence of ochratoxin A in blood. This conclusion is based on 1675 samples and 147 standards analysed concurrently by the flow injection technique and an earlier published enzymic method. The method is also suitable for monitoring ochratoxin A levels in the blood of experimental animals.
The effects of disulfiram on the experimental C3H mouse embryo
Authors: Thompson P. A. C. , Folb P. I. 
Published: October 2006

AbstractDisulfiram, in 1 mg and 10 mg oral doses, was given to inbred C3H mice prior to and for the duration of pregnancy. The effects on the fetus have been assessed at 18 days gestation by means of fetal and placental weights, number of resorptions, skeletal preparations and Wilson's sections. Disulfiram dissolved in diethyl ether was administered to 8‐ and 9‐day embryos in vitro in concentrations of 0.1, 10 and 100 μgml−1 of culture medium, and the effects of ether alone and ether plus disulfiram assessed by evaluation of morphological development over a 28‐h period, and inhibition of DNA synthesis using tritiated thymidine labelling over a 4‐h period. Disulfiram (1 mg) in vivo caused no adverse effects on the fetus, but disulfiram (10 mg) was toxic, in that it caused a significant increase in early resorptions. Disulfiram in vitro, in the 10 and 100 μg ml−1 concentrations, proved to be very toxic to the embryos, affecting both morphological development and DNA synthesis in 9‐day embryos and morphological development in 8‐day embryos. DNA synthesis was only inhibited at the 100 μg ml−1 concentration in 8‐day embryos. The 0.1 μg ml−1 concentration of disulfiram caused abnormal central nervous system development in 8‐day embryos, but was otherwise non‐toxic to 8‐ and 9‐day embryos. Apart from a reduction in somite counts, ether in concentrations of 0.285 mg ml−1 and 2.85 mg ml−1 caused no adverse effects on morphological development in 8‐ or 9‐day embryos. DNA synthesis was inhibited by ether in a concentration of 2.85 mg ml−1 in 9‐day embryos.
Lethality in mice and rats exposed to 2450 mhz circularly polarized microwaves as a function of exposure duration and environmental factors
Authors: Berman E. , Kinn J. B. , Ali J. , Carter H. B. , Rehnberg B. , Stead A. G. 
Published: October 2006

AbstractAdult male CD‐1 mice and CD rats were used to determine LD50/24 h lethality rates from exposure to 2450‐MHz circularly polarized microwaves. Groups of 16 mice or six rats were exposed in each of 32 combinations of nominal power density (10, 25, 50 or 75 mW cm−2), exposure duration (1 or 4 h), and environmental temperature (20 or 30 °C) and relative humidity (35 or 80%). An analysis of variance probit model was used to determine the influence each variable had on the probability of death. Significant factors in lethality were nominal power density, exposure duration and environmental temperature, but not environmental relative humidity. The estimated power density (mW cm−2) required to kill 50% of the animals in 24 h is halved when the environmental temperature is increased from 20 to 30 °C. Similarly, only 20–25% of the power density is required when the exposure duration is increased from 1 to 4 h. The use of nominal power density as a predictor of the probability of death was more efficient than specific absorption rate estimated experimentally by twin‐well calorimetry. The exposure of one mouse at a time, instead of 16, did not alter the predicted death rate.
Adenosine triphosphatase activities in plasma liver membranes of rats treated with DDT and toxaphene
Authors: Mourelle Marisabel , Garcia Martha , Aguilar Carolina 
Published: October 2006

AbstractThe effect of exposure to chlorinated insecticides (DDT and toxaphene) on Na+, K+‐ATPase, Mg2+‐ATPase and Ca2+‐ATPase activities of the plasma membrane of hepatocytes was determined. Acute treatment with DDT (200 mg per kg body weight) or toxaphene (110 mg per kg body weight) produced a significant decrease in Na+, K+‐ATPase activity (80% and 85%, respectively) 24 h after treatment. DDT also produced a 30% decrease in Mg2+‐ATPase and Ca2+‐ATPase activity, but toxaphene treatment did not modify these enzymes. The effect of exposure to daily doses of DDT (30 mg per kg body weight) or toxaphene (16.5 mg per kg body weight) for a period of 3.5 months was also studied. Animals were sacrificed at 15‐day intervals and results showed that Na+, K+‐ATPase activity decreased 80% from the beginning of each treatment and the activity remained low throughout the treatment period. DDT, but not toxaphene, also led to a decrease in Mg2+‐ATPase (20%) and Ca2+‐ATPase (35%) activity. The low values observed from the beginning remained low throughout the treatment period. We believe that the general mechanism of ATPase inhibition by organochloride compounds could be the result of its interaction with membrane lipid components, although some differences could arise from differences in their spatial structure.
Effects of bleomycin on 14C‐proline uptake, its incorporation into proteins and hydroxylation in collagenous proteins of hamster lung slices
Authors: Giri Shri N. , Younker Wanda R. , Schiedt Mary J. 
Published: October 2006

AbstractThe uptake of 14C‐proline by lung slices and its incorporation into trichloroacetic‐acid (TCA)‐insoluble proteins and hydroxylation in collagenous proteins were studied. They were found to be linearly increased with the incubation time for as long as 8 h. The effects of different concentrations of bleomycin on these parameters were subsequently investigated. Bleomycin at 10−3M significantly reduced the uptake of 14C‐proline to 75% of the control value. The incorporation of 14C‐proline into TCA‐insoluble proteins was reduced to 84%, 78% and 75% of the control at 2.5 × 10−4M, 5 × 10−4M and 10−3M concentrations of bleomycin, respectively. Bleomycin failed to alter the proline pool size of the lung slices at any of these concentrations. In addition, bleomycin also inhibited the hydroxylation of 14C‐proline into collagen to 72% and 69% of the control at 5 × 10−4M and 10−3M, respectively. These findings show that bleomycin‐induced increases in collagen synthesis in vivo is probably secondary to inflammatory reactions of the lung and bleomycin per se has little effect on increased collagen synthesis responsible for lung fibrosis.