bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of hepatic function and damage in animal species. A review of the current approach of the academic, governmental and industrial institutions represented by the Animal Clinical Chemistry Association
Authors: Woodman D. D.
Published: October 2006

There are a wide variety of laboratory tests available to assess damage to and functional impairment of the liver, though the effectiveness of these tests varies greatly depending upon the type of damage and the animal species involved.

Species differences in tissue localization, metabolism, specificity and sensitivity of parameters relating to the liver influence the choice of tests. Some tests can be applied usefully to most animal species while others may be highly specific in one species but show very low discriminatory potential in others.

The tests available, and their use in veterinary and toxicological investigations have been reviewed in the light of current practice in the U.K.
Prevention of cadmium‐induced effects on regional glutathione status of rat brain by vitamin E
Authors: Shukla Girja S. , Srivastava R. S. , Chandra S. V.
Published: October 2006

The effect of vitamin E on the cadmium‐induced changes of glutathione metabolism was investigated in different brain regions. Daily intraperitoneal injection of cadmium (0.4 mg/kg) for 30 days significantly decreased the concentration of reduced glutathione (GSH), and the activities of glutathione reductase (GR) and glucose‐6‐phosphate dehydrogenase (GPDH) in the cerebellum, cerebral hemispheres and brain stem of rats. Cadmium elevated the levels of oxidized glutathione (GSSG) in cerebellum and cerebral hemisphere regions only, while the GSH/GSSG ratio decreased in all three brain regions. The only effect of intramuscular injections of vitamin E (5 mg/kg) given on alternate days for 30 days was a slight increase in GSH and GR in the cerebral hemispheres. The simultaneous administration of vitamin E and cadmium prevented cadmium‐induced changes in GSH and GSSG levels and in the GSH/GSSG ratio, but the cerebellar GSH remained lowered. Furthermore, vitamin E, with the exception of GR in the cerebral hemispheres, did not prevent cadmium‐induced changes in enzyme activities. As the simultaneous injections of vitamin E reduced cadmium‐induced alterations in glutathione concentration without having any appreciable effect on the activity of related enzymes, it is suggested that the preventive effect of vitamin E is mediated through its antioxidative effect, saving GSH from oxidative destruction in the brain of cadmium‐exposed rats.
A protocol to evaluate the fibrogenic potential of inhaled materials
Authors: Bennett I. P. , Pigott G. H. , Isaacs K.
Published: October 2006

A protocol to provide a more rapid assessment of the fibrogenic potential of an inhaled particulate has been developed. Young rats are exposed nose‐only for 6 h/day, 7 days a week for 28 days to a respirable aerosol of the test compound. After exposure the rats are kept for up to 1 year, followed by histopathological assessment of the lung. Interim sacrifices could allow an estimate of the rate and severity of the development of any fibrogenic lesion.

The protocol has been evaluated for chrysotile asbestos, α‐quartz and titanium dioxide using rats of both sexes and two different ages at first exposure. The results indicate that there are no significant differences in either the rate, type or extent of lesion provoked by a 28‐day exposure period when compared with the more conventional 1‐year exposure period studies. It can be concluded that neither sex nor age at first exposure cause any biologically significant differences in response, although young rats would be used in practice. Only one sex need be investigated.

The protocol offers considerable benefits over conventional inhalation studies for fibrogenicity (where a 1‐year exposure period followed by a further 1‐year holding period is usual) by virtue of time, specificity (in the absence of continued exposure the development of any lesion can be studied free from initial inflammatory response) and cost, and could be incorporated into a standard subacute inhalation study design.

The results obtained are also of more physiological relevance than studies based on intratracheal instillation.
Methodological aspects of the determination of the acute inhalation toxicity of spray‐can ingredients
Authors: Pauluhn J. , Machemer L. , Kimmerle G. , Eben A.
Published: October 2006

Spray‐can ingredients, if liberated in confined spaces, are potential health hazards for man. Thus, appropriate inhalation toxicity studies have to be performed in accordance with internationally recognized guidelines, e.g. the US Environmental Protection Agency: Federal Insecticide, Fungicide and Rodenticide Act (FIFRA no. 81–3) or OECD no. 403.

One of the essential requirements of such guidelines is that test animals (preferably rats) be exposed to a steady‐state concentration in a dynamic inhalation chamber for at least 4 hours. This is not easy to achieve with vapours released from a pressurized spray‐can.

The method described here makes it possible to expose experimental animals in an inhalation chamber to a steady‐state concentration of intermittently released spray jets of constant doses per jet. Animal experiments and theoretical considerations (computer simulations) have shown that the method presented allows an up‐to‐date determination of the acute inhalation toxicity of spray‐can ingredients.
Effect of cimetidine on hepatic biochemical changes, liver toxicity and major urinary metabolite excretion of trichloroethylene in rats
Authors: Landriault Helene , Sirois Gerard , Chakrabarti Saroj , Cote Michel G.
Published: October 2006

The effects of cimetidine (CIM) (an inhibitor of the hepatic microsomal monooxygenase system) on the metabolism and hepatotoxicity of trichloroethylene (TRI) were studied in male Sprague‐Dawley rats. Rats were given three doses of 120 mg/kg i.p. (low‐dose regimen) of CIM at 0, 6 and 11 h for 1 day, or ten doses of 200 mg/kg (high‐dose regimen) at 8, 11, 14 and 17 h for 2 days and 8 and 11 h on 3rd day. Trichloroethylene (0.5 or 0.65 ml/kg) was administered i.p. 1 h after 2nd dose (low‐dose regimen) or 9th dose (high‐dose regimen) of CIM. In the low‐dose regimen study, the activity of hepatic microsomal aminopyrine N‐demethylase was decreased 1 and 5 h after the second dose and 7 h after the third dose of CIM, but became normal 20 h after the last dose. The cytochrome P‐450 content and the activities of aniline hydroxylase and epoxide hydratase remained unchanged. Trichloroethylene at both dose levels produced liver toxicity, as verified by increase in activities of SDH and SGPT as well as by liver histology. Cimetidine alone had no such effect. An apparent reduction in TRI toxicity by CIM (at both dose regimens) could be observed histologically. The biochemical tests (SDH and SGPT) corroborated the histological changes only when TRI was given at a dose of 0.5 ml/kg combined with a high‐dose regimen of CIM. Cimetidine at both dose regimens had a tendency to decrease the in vivo metabolism of TRI. These results therefore indicate that CIM may have a short‐lived inhibitory effect on the hepatic mixed‐function oxidase system, resulting in some protective effect on TRI hepatotoxicity.
Toxicokinetics of ochratoxin A in several species and its plasma‐binding properties
Authors: Hagelberg Sigrid , Hult Karl , Fuchs Radovan
Published: October 2006

The toxicokinetic profile of ochratoxin A was studied after the oral or intravenous administration of 50 ng/g b.w. to fish, quail, mouse, rat and monkey. The elimination half‐life varied from 0.68 h after oral administration to fish, up to 840 h after intravenous administration to monkey. The distribution volume ranged from 57 ml/ kg in fish to 1500 ml/kg in quail. The plasma clearance was most rapid in quail and fish, 72 and 58 ml/kg·h, respectively, while it was only 0.17 ml/kg·h in monkey. The bioavailability was as low as 1.6% in fish but as high as 97% in mouse.

The binding abilities of ochratoxin A to plasma proteins were also studied. From these data we calculated the free fraction of toxin in plasma, which we found to be < 0.2% in all species investigated (including man) except fish.

A similar but smaller investigation on the toxicokinetics and binding properties of ochratoxin B was also performed. Ochratoxin B was more readily eliminated and had a lower affinity for plasma protens, which partly may explain its lower toxicity.
A combined testing protocol for assessing genotoxicity in individual animals: Application to environmental toxicology
Authors: Harper Barbara L. , Ward Jonathan B. , Ramanujam V. M. Sadagopa , Ammenheuser Marinel M. , Au William W. , Moslen Mary Treinen , Legator Marvin S.
Published: October 2006

A multiple end‐point approach to assessing genetic toxicity (the combined testing protocol, CTP) was evaluated in male and female CD‐1 mice exposed subacutely (3 and 6 weeks) to low levels of a custom‐blended gas mixture (epichlorohydrin, benzene, chloroprene and xylene, at 50, 100, 100, and 100 ppb, respectively, as the low dose, with concentration levels 10‐fold and 100‐fold higher as the intermediate and high doses, or 0.1, 1 and 10 ppm of benzene). Urine mutagenicity was tested in the Salmonella/microsome assay, chromosome aberrations were examined in bone marrow and spleen lymphocytes, micronuclei were measured in bone marrow and peripheral erythrocytes, and cytochrome P450 and glutathione S‐transferases were measured in the liver. Structural aberrations in alveolar macrophages and spermatocytes, and thioguanine resistance in spleen lymphocytes were examined for their suitability for incorporation into the overall protocol.

Spleen lymphocytes were the most sensitive indicator cells, and showed a dose‐related increase (P<0.01) in structural chromosome aberrations and in cytotoxicity after 6 weeks of exposure. Analysis of micronucleus formation and metaphase aberrations in the bone marrow, and micronuclei in peripheral erythrocytes showed an overall statistically non‐significant but positive trend at the high dose. No mutagenicity was detected in pooled urine samples. Liver microsomal cytochrome P450 was not increased, but cytosolic glutathione S‐transferases were significantly increased in a dose‐related manner. Since the probability of detecting a genotoxic effect increases with the number of endpoints and tissues examined, this approach should be applicable to many situations without having to perform separate experiments for each tissue examined. The multiple endpoints evaluated and the flexibility of the CTP with respect to which endpoints are included, plus the reduction in experimental variability, give it advantages over batteries of separate assays.
Cadmium toxicity and bioantioxidants: Status of vitamin E and ascorbic acid of selected organs in rat
Authors: Shukla Girja S. , Chandra S. V.
Published: October 2006

Effects of i.p. administered cadmium acetate (Cd, 0.4 mg/kg) was studied on the levels of vitamin E and ascorbic acid in different brain regions, liver, kidney, testis, RBC and plasma at 15, 30 and 60 days intervals in male albino rats (45 ± 5 g). Exposure to Cd for 15 days decreased the levels of vitamin E significantly in the liver and testis only, while 30 days of treatment resulted in a signifcant decline in cerebellum, cerebral cortex, corpus striatum, mid‐brain + hypothalamus, and plasma. Cadmium administration for 60 days caused a decrease in vitamin E in all tissues. Furthermore, a duration‐dependent decrease in hepatic ascorbic acid levels was noticed. The implications of these results are discussed.
Relative metabolism of quinones to semiquinone radicals in xanthine oxidase system
Authors: Lewis David C. , Shibamoto Takayuki
Published: October 2006

Rates of enzymatic single‐electron reduction of some myotoxc quinones to semiquinone metabolites in an in vitro xanthine oxidase/hypoxanthine/catalase system varied widely. Naphthoquinones, especially juglone, were found to undergo rapid single‐electron reduction. Benzoquinones and benzoquinoneimines, as well as phenanthrene‐9,10‐quinone, benzo[a]pyrene‐3,6‐quinone, and diethylstilbestrolquinone, were also actively reduced. The anthraquinones danthron, doxorubicin and emodin were poorly metabolized in this system. N‐Acetylcysteine inhibited quinone‐stimulated cytochrome C reduction at high concentrations. The results of this study are discussed with respect to cytotoxicity and mutagenicity of selected quinones.
Bioreactivity of intratracheally administered slate dust in rats: Incorporation of 14C‐acetate into lung lipids
Authors: Khan M. Firoze , Ali Shahid , Rahman Qamar
Published: October 2006

The effect of intratracheally instilled slate dust on the phospholipid profile, and 14C‐acetate incorporation into the lipids of lung lavage, whole lung tissue and its subcellular fractions, has been studied in rats. The acellular fraction of lung lavage showed a decrease in the phospholipid content at 4 days and then an increase at 40 days of dust exposure, whereas the cellular fraction showed the reverse. The order of 14C‐acetate incorporation into total lipids and individual phospholipids showed a parallel trend. The rate of incorporation with total lipids of lung tissue was higher at the two stages of dust exposure and a similar pattern prevailed in the subceiiuiar fractions, i.e. mitochondrial, microsomal and cytosolic fraction. Acetate incorporation was highest in mitochondria, followed by the microsomes. An increase in the microsomal and mitochondrial cholesterol levels was also observed. There was no significant change in the solvent‐extracted 14C‐counts of whole plasma, trichloroacetic acid (TCA) precipitate and TCA supernatant of plasma. The results indicate that slate dust causes an enhanced synthesis of pulmonary surfactant and other lung lipids and, therefore, has an effect on the metabolism of type II alveolar epithelial cells.
Chlordecone (kepone®)‐potentiated carbon tetrachloride hepatotoxicity in partially hepatectomized rats — a histomorphometric study
Authors: Kodavanti Prasada Rao S. , Joshi Urmila M. , Mehendale Harihara M. , Lockard Virginia G.
Published: October 2006

Our previous studies indicated the involvement of some unidentified mechanisms, apart from the bioactivation phenomenon, in chlordecone (CD)‐potentiated CCl4 hepatotoxicity and lethality. Recent studies revealed that hepatocellular regeneration is suppressed in CD + CCl4 toxicity. The present work is a continuation of our earlier work employing a partial hepatectomy model for stimulating hepatocellular division, in normal (N) or CD‐treated (10 ppm for 15 days) rats. Male Sprague‐Dawley rats maintained on an appropriate dietary protocol and undergoing sham (SH) or partial hepatectomies (PH) were employed. Hepatocellular regeneration was assessed by measuring the percentage mitotic figures and by autoradiography of liver sections from rats given 3H‐thymidine in vivo. Hepatotoxicity was assessed by examining liver sections for necrotic cells, swollen cells and cells having lipid droplets. CCl4 (100 μl kg−1)‐induced histopathological alterations in CD‐pretreated rats were significantly decreased in rats 2 days post‐PH (PH2) as compared to SH rats or rats 7 days post‐PH (PH7), indicating that amplification of CCl4 toxicity is significantly reduced when there is a greater regenerative activity. The percentage of mitoses as well as the percentage of labelled cells were significantly elevated at 2–6 h after CCl4 administration in N rats but remained suppressed in CD rats. In CD‐pretreated PH2 rats where the percentage of mitoses and the percentage of labelled cells were many‐fold greater when compared to SH or PH7 rats, a portion of the stimulated hepatocellular division decreased significantly at 2–6 h after CCl4 administration, but remained significantly greater when compared to basal level of regeneration. These results support our concept that suppression of hepatocellular regeneration is one of the events responsible, besides the bioactivation phenomenon, for the CD‐potentiated CCl4 hepatotoxicity.
Dose‐related proximal tubular dysfunction in male rats chronically exposed to lead
Authors: Vyskocil Adolf , Pancl Jan , Tusl Miloslav , Ettlerova Eva , Semecky Vladimir , Kašparová Lucie , Lauwerys Robert , Bernard Alfred
Published: October 2006

Male Wistar rats were given 0.5 and 2% lead acetate in drinking water for 2 months, 1% lead acetate for 3 months and sodium acetate equimolar to 2% lead acetate for 3 months. Glucose, total proteins, lactate dehydrogenase (LDH), lysozyme and β2‐microglobulin (β2‐m) were measured in 24‐h urine every month. Kidney weight and histology were also examined.

At the three doses, lead exposure produced a significant elevation of the kidney weight. No significant change in urinary parameters was observed in rats given 0.5% lead acetate. Exposure to 1% lead acetate increased the urinary excretion of β2‐m only.

At the 2% lead acetate dose the elevation of β2‐m excretion was accompanied by an increased urinary output of glucose, total proteins, lysozyme and LDH. Observations of the kidneys by light microscopy were in agreement with these biochemical findings. The nephrotoxic effect of acetate was excluded by the lack of biochemical or histological effects of sodium acetate on the kidney. It is concluded that a proximal tubular dysfunction is induced in rats chronically exposed to high doses of lead.
The effect of 2,4‐dichlorophenol on growth and plasmidic β‐lactamase activity in Escherichia Coli
Authors: Espigares M. , Mariscal A.
Published: October 2006

The toxic effects of 2,4‐dichlorophenol on two strains of Escherichia coli harbouring plasmids with β‐lactamase activity were studied. The toxicant had a significant effect on growth at concentrations of 12 μg ml−1 for the JA 221 (pBR322) strain, as well as at 24 μg ml−1 for the J5‐3 (RP4) strain. β‐Lactamase production was affected at concentrations of 96 μg ml−1 in both strains. However, β‐lactamase production does not seem to constitute a reliable toxicity test in view of its variability and relatively low sensitivity.
Measurements of cardiopulmonary response in awake rats during acute exposure to nearambient concentrations of ozone
Authors: Tepper Jeffrey S. , Wiester Mildred J. , Weber Mary F. , Ménache Margaret G.
Published: October 2006

Cardiopulmonary responses during acute exposure to near‐ambient (< 1.0 ppm) concentrations of ozone (O3) have not been reported for the unanesthetized rat. Such data on species sensitivity are crucial for the extrapolation of animal data to man. Therefore, this study was conducted to obtain functional measurements on awake rats using head‐out plethysmographs and intrapleural or carotid artery catheters during a 135‐min exposure to 0.0, 0.12, 0.25, 0.5 or 1.0 ppm O3. Carbon dioxide was added during alternate 15‐min periods of the exposure to increase ventilation, much like the use of exercise in human O3 exposure studies. The results established that frequency of breathing was increased and tidal volume was decreased as a function of both the concentration and the duration of exposure. Breathing mechanics and cardiopulmonary measures were only marginally affected. Differences in the response of individual rats revealed that as O3 concentration increased, the proportion of rats responding and the magnitude of the response was increased. These data indicate that, for similar functional responses, the rat's sensitivity to O3 is comparable to that observed in man.
Cardioteratogenic dose of ethanol in the chick embryo results in egg white concentrations comparable to human blood alcohol levels
Authors: Bruyere Harold J. , Kapil Ram P.
Published: October 2006

Three‐day‐old chick embryos were exposed to a dose of ethyl alcohol (0.32 ml of 50% ethanol) that we previously demonstrated produces cardiac malformations in 96.6% of the animals. Ethanol was administered into the air sac at 72–80 h of incubation. Samples of egg white were drawn at 2, 6 and 24 h after treatment and analyzed by capillary gas–liquid chromatography. Ethanol concentrations were significantly higher at 6 and 24 h after exposure than at 2 h (P < 0.01), but there were no differences in mean concentrations between 6 and 24 h (P > 0.2). Furthermore, concentrations (43–303 mg dl−1) were comparable to human blood alcohol levels during intoxication. These results suggest that the cardioteratogenic doses of ethanol administered to chick embryos in a previous study are not excessive in terms of potential human embryo exposure.
Acetylation of 5‐aminosalicylate by hamster colon arylamine N‐acetyltransferase
Authors: Tucker Mark A. , Smith Timothy J.
Published: October 2006

Recent evidence suggests that 5‐aminosalicylate acts as an anti‐inflammatory agent by virtue of its ability to act as a free‐radical scavenger. The major metabolite, N‐acetyl‐5‐aminosalicylate is not an effective free‐radical scavenger. We have demonstrated that an arylamine N‐acetyltransferase from hamster colon can directly acetylate 5‐aminosalicylate, suggesting that the colon may have the ability to modulate the activity of this agent through metabolic inactivation.
Differential mutagenicity of two dihydrophenalene congeners: Examination of formaldehyde generation and reactive intermediate formation as possible mechanisms
Authors: Petry T. W. , Jolly R. A. , Aaron C. S. , Schwende F. J.
Published: October 2006

Compounds in the dihydrophenalene series are currently under investigation as potential antipsychotic agents. The mutagenicity of two compounds in this series was evaluated in several strains in the Ames Salmonella assay with and without S9 activation. U‐65,556A (2,3‐dihydro‐N,N‐dimethyl‐1H‐phenalen‐2‐amine HCI) was less mutagenic than its monomethyl analogue, U‐64,273A. Two hypotheses—the release of formaldehyde and the formation of macromolecular reactive intermediates—were evaluated as possible mechanisms for the observed mutagenicity. Formaldehyde release during biotransformation of U‐65,556A but not U‐64,273 was demonstrated, as measured by trapping with the Nash reagent. Thus, formaldehyde release does not correlate with the mutagenic potency of these compounds. Covalent binding of U‐65,556A‐[3H] equivalents to rat hepatic protein was observed, but binding to DNA, which is considered the more critical target molecule, was not observed. These data suggest that reactive intermediate formation does not explain the mutagenicity of U‐65,556A in the Ames Salmonella assay. Follow‐up studies were conducted to assess the possible contribution of tritium exchange to the observed covalent binding to protein by quantitatively recovering 3H2O from incubations containing U‐65,556A‐[3H] and rat liver microsomes. Data indicate that enzyme‐dependent formation of 3H2O does occur but that this phenomenon does not account for U‐65,556A‐[3H]‐derived, proteinbound tritium in covalent binding studies.
Toxicity of 2‐methyl‐5,6‐cyclopentapyrimidine (MCPP)
Authors: Kennedy Gerald L.
Published: October 2006

2‐Methyl‐5,6‐cyclopentapyrimidine (MCPP, CAS No. 36274–29–0) is a white dusty solid with a powerful lingering odor and is formed as a by‐product in the polymer synthesis of an experimental polymer. The acute toxicity following both oral and inhalation exposures and the effects of repeated inhalation exposures in rats were determined. Mutagenic activity was assessed using Salmonella as the indicator organism. The chemical is moderately toxic, with the lethal dose following a single oral administration being 90 mg kg−1. Doses ≧ 130 mg kg−1 produced strong convulsions. Excessive salivation, hyperactivity and twitching were seen at 90 mg kg−1 and only mild initial weight loss was seen in surviving rats (≦ 60 mg kg). Liver injury was produced at doses as low as 17 (but not at 12) mg kg−1. The material was highly toxic by inhalation, with the approximate lethal concentration in rats following single 4‐h exposures being 9 ppm. Convulsive‐like movements were seen at ≦ 9 ppm (not at 2 ppm). Histological findings suggest that MCPP causes dilation of blood vessels with hyperemia of various organs apparent in rats exposed to 1 ppm and sacrificed 1 or 2 days post‐exposure. No evidence of liver or central nervous system damage was seen. Repeated (nine daily 4‐h exposures) inhalation of 2 ppm MCPP failed to produce any signs of a toxic response. No mutagenic activity was seen. The material needs to be considered as a potent acute toxin.
Calcium antagonists can be classified using in vitro toxicity and potency indices
Authors: Shrivastava Ravi , John Gareth , Massingham Roy
Published: October 2006

The toxicity of eleven calcium antagonists from different chemical families was determined in rat hepatocyte primary cultures. The calcium antagonist potency of the same compounds was also determined in isolated rabbit aortic rings contracted with high K+. The hepatocytotoxicity of the calcium antagonists was not directly linked to blockade of voltage‐operated calcium channels, since there was no correlation between the rank order of hepatotoxicity and that for calcium antagonist potency. The toxicity and calcium antagonist potency of each calcium antagonist examined were used to calculate an in vitro therapeutic index value for each compound. It was observed that therapeutic indices fell into three distinct groups and we therefore propose that the in vitro therapeutic index can be used to subclassify the calcium antagonist group of drugs. The proposed classification corresponds very closely with one already suggested by Spedding on pharmacological grounds. In conclusion, the in vitro therapeutic index may provide a useful tool in the characterization and subclassification of novel calcium antagonist compounds.
The Ca2+‐transport‐atpase of human erythrocytes as an in vitro toxicity test system—acute effects of some chlorinated compounds
Authors: Janik F. , Wolf H. U.
Published: October 2006

Investigations to determine the inhibitory activity on the Ca2+‐transport‐ATPase of human erythrocyte membranes were performed with various compounds of toxicological significance, mostly chlorinated and mainly used as biocides, such as phenol, 4‐chlorophenol. 2,4‐dichlorophenol, 2,6‐dichlorophenol, 3,4‐dichlorophcnol, 2,3,4‐trichlorophenol, 2,3,4,5‐tetrachlorophenol, pentachlorophenol (PCP), captan, folpet, captafol, (+)‐camphene, toxaphene, dichlorodiphenyltrichloroethane (UDT), lindane, endrin, dieldrin, α‐endosulfan, β‐endosulfan, paraquat, diallate, 2,4‐dichlorophenoxyaceticacid (2,4‐D) and 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T).

Some of the compounds investigated display an inhibitory effect on the Ca2+‐transport‐ATPase at very low concentrations. The in vitro results obtained in this enzyme assay can be correlated directly with the results of other in vitro assays and with the results of in vivo investigations in different species in whkh an inhibitory effect on various biological functions is observed. Therefore, an inhibitory effect on the Ca2+‐transport‐ATPase indicates a toxic effect of these compounds to cell functions.

Since the inhibitory effect of these compounds can be measured rapidly and the enzyme is easy to handle, it might be a useful tool to screen the toxic effects of various compounds on cell function. The aim of the authors was to investigate the usefulness of this screening test system for the characterization of the cellular toxicity of various compounds.
Haematological and hepatotoxic effects of silken styles of corn in albino rats
Authors: Garg D. K. , Goyal R. N.
Published: October 2006

The alterations of haematological parameters in albino rats were studied after oral administration of an aqueous extract of silken styles of corn (Zea maize Linn.) at 50, 100 and 150 mg kg−1 daily for 21 days. The following haematological values were significantly reduced on the 7th and 21st day following extract administration: haemoglobin (Hb), red blood corpuscles (RBC), clotting time (CT), mean corpuscular volume (MCV), haematocrit (Ht), serum glucose, blood urea nitrogen (BUN), cholesterol, aspartate transaminase (AST), alanine transaminase (ALT), calcium, total protein, total albumin and total acid phosphatase; and white blood corpuscles (WBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), alkaline phosphatase and creatinine increased. The remaining parameters were not significantly affected, except body weight parameters at the two highest doses.

The results emphasize that the biochemical changes caused through aqueous extract of silken styles of corn (Zea maize Linn.) are not significantly toxic at low and medium doses (50 and 100 mg kg−1).
Effects of 3‐methylcholanthrene or diethyl maleate on the hepatotoxicity of acetaminophen
Authors: Szymańska J. A. , Swietlicka E. A. , Piotrowski J. K. , Skrzypińska‐Gawrysiak M. , Sporny S.
Published: October 2006

This report presents a set of investigations on the hepatotoxic action of acetaminophen (AA). Male mice of Balb C strain were given [3H]acetaminophen in doses of 100, 300 and 600 mg kg−1 with or without pretreatment with 3‐methylcholanthrene (3MCh) or diethyl maleate (DEM).

The results of this study show that AA administered in moderate doses brings about necrotic changes due to adduct formation with macromolecules. Adduct formation was inversely correlated with the level of glutathione.

Both modifiers enhanced hepatic necrosis and lethality. Diethyl maleate exerted these effects without enhancing covalent binding to macromolecules, while 3MCh increased both adduct formation and lipid peroxidation.
The pathological effects of glove and condom dusting powders
Authors: Kang N. , Griffin D. , Ellis H.
Published: October 2006

Dusting powders are used on latex gloves and condoms. They help to release these products from their moulds during manufacture and facilitate processing and donning. Dusting powders are also used on contraceptive diaphragms, sanitary napkins and in toiletries. There are numerous dusting powders in current use around the world. At present a consensus exists about the best dusting powder to use on surgical gloves, based on data about the safety of these agents in humans, as well as their manufacturing qualities. No such consensus exists for the use of dusting powders in other situations. However, there is uncertainty about whether dusting powders used in situations other than on surgical gloves are responsible for harmful effects. This study uses intraperitoneal injections in rats to examine the pathological effects of dusting powders that are in current use on surgical gloves and condoms. We suggest that dusting powders may be a source of morbidity when used in situations other than on surgical gloves and confirm the findings of previous investigators that the dusting powders we tested differ in their ability to produce pathological effects.
Spontaneous renal neoplasms in rats
Authors: Chandra M. , Riley M. G. I. , Johnson D. E.
Published: October 2006

Spontaneous renal neoplasms in the rat are uncommon. This paper presents the incidence and histopathological features of various long‐term developing renal tumors observed in control rats from 17 carcinogenicity studies (1340 males and 1329 females) in Sprague‐Dawley rats and 10 carcinogenicity studies (530 males and 530 females) in Fischer‐344 (F‐344) rats. Renal cell adenoma (0.08% in Sprague‐Dawley and 0.28% in F‐344), lipoma/liposarcoma (0.37% in Sprague‐Dawley and 0.75% in F‐344) and transitional cell carcinoma (0.07% in Sprague‐Dawley and 0.09% in F‐344) were observed in both Sprague‐Dawley (0.49%) and F‐344 (1.13%) rats. Pulmonary metastasis was observed from one case of transitional cell carcinoma. Renal cell carcinoma with metastasis to the lung and liver was seen in one F‐344 rat. In addition, transitional cell papilloma and nephroblastomas were also observed in Sprague‐Dawley rats. Metastases from nephroblastoma were seen in the lungs and renal lymph node in two cases. In both rat strains, the tumor incidence was higher in males than in females.
Sensory and pulmonary irritation of aliphatic amines in mice: A structure–activity relationship study
Authors: Gagnaire F. , Azim S. , Simon P. , Cossec B. , Bonnet P. , de Ceaurriz J.
Published: October 2006

The expiratory bradypnea indicative of upper airway irritation in mice was evaluated during a 15‐min oronasal exposure to increasing concentrations of sixteen aliphatic amines. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each test compound. Moreover, the sixteen amines were tested for pulmonary irritation by measuring the decrease in respiratory rate of (non‐anaesthetized) tracheally cannulated mice (RD50 TC). The RD50 and RD50 TC values and their ratios were related to n‐octanol/water partition coefficients (log P). The RD50 values associated with exposure to saturated amines ranged from 17 to 300 ppm. The RD50TC values for these saturated amines ranged from 35 to 489 ppm. The RD50 and RD50TC values of saturated amines were closely related to the n‐octanol/water partition coefficient, indicating that the more lipophilic amines are more irritant for the upper and lower respiratory tracts. The RD50TC/RD50 values were much less closely related to the n‐octanol/water partition coefficient.

Based on the results, tentative standards are suggested for the studied amines.
Dibromomethane and carbon monoxide in the rat: Comparison of the cardiovascular and metabolic effects
Authors: Fozo Michael S. , Penney David G.
Published: October 2006

The goals of this study were to examine the cardiovascular and metabolic responses to a dihalogenated methane and to compare them to inhaled CO. One group of male Sprague‐Dawley rats received an i.p. injection of either 3 or 6 mmol kg−1 dibromomethane (DBM) diluted 1:3 with sesame oil. Measurements of carboxyhemoglobin (COHb), rectal body temperature (BT), heart rate, systolic blood pressure (BP) and blood glucose and lactate concentrations were made at times 0, 30, 60, 120, 240, 360, 480, 600, 720, 840, 1020, 1440 and 1680 min. A second group of rats received only sesame oil and was tested in the same manner. A third group of rats breathed 225 ppm CO for 120 min before being tested. Peak COHb levels were 16% 8 h after 3 mmol kg−1 DBM, 18% 12h after 6 mmol kg−1 DBM and 17% in the CO‐exposed group. The sesame oil controls exhibited no elevation in COHb. The BT dropped by ca. 1°C in both the DBM‐ and CO‐exposed rats, while there was no BT change in the sesame oil controls. The BT dropped by 1.0°C and 1.2°C after 6h in the 3 and 6 mmol kg−1 DBM groups, respectively, and by 0.9°C after 120 min in the CO‐exposed group. The CO‐exposed rats displayed a 12 mmHg decrease in systolic BP, while both doses of DBM failed to produce any significant BP change. The BP in the sesame oil controls remained constant. There were no significant changes in heart rate or in blood glucose or lactate in any of the experimental groups. The lack of a BP response in the DBM rats may be due to DBM interferring with the rat's normal response to CO, or to the effects of dissolved CO vs. COHb. Dibromomethane uptake results in the development of significant and prolonged COHb saturation, at a level similar to that resulting from inhalation of 225 ppm CO. Although BT regulation is impaired, DBM appears not to have significant effects on BP, heart rate or blood glucose and lactate concentrations.
Cimetidine prevents and partially reverses CCl4‐induced liver cirrhosis
Authors: Muriel Pablo , Mera Elvia , Castillo Carlos , Mourelle Marisabel
Published: October 2006

Liver injury produced by CCl4 depends on its metabolism by the liver cytochrome P450 enzyme system to a highly reactive intermediate (CCl3·). Cimetidine impairs cytochrome P450 and stimulates regenerative processes acting on DNA synthesis. This work was performed to investigate whether cimetidine may prevent CCl4‐induced liver cirrhosis. Male Wistar rats were used: animals in group 1 received CCl4 (0.04 g per 100 g, i.p.) three times a week for 8 weeks; group 2 was treated with CCl4 plus cimetidine (120 mg kg−1, p.o.) three times a week for 8 weeks; group 3 received CCl4 for 8 weeks and then cimetidine for 4 weeks. Alkaline phosphatase, γ‐glutamyl transpeptidase (γ‐GTP) and alanine aminotransferase (ALT) activities, as well as protein and bilirubin, were measured in serum; collagen and lipoperoxidation were quantified in liver. Intoxication with CCl4 increased (P < 0.05) serum activities of alkaline phosphatase, γ‐GTP and ALT, and bilirubin concentration; liver collagen and lipoperoxidation were also increased. Cimetidine treatment prevented or reverted the increases in the three enzyme activities and in bilirubin content and the fall in proteins. It is worth noting that cimetidine co‐treatment completely prevented both the increase in collagen content and the lipid peroxidation. The protective effect of cimetidine can be attributed to a reduction in cytochrome P450. However, it could also stimulate regenerative processes.
Hemolysis and deformability of erythrocytes exposed to butoxyacetic acid, a metabolite of 2‐Butoxyethanol: II. Resistance in red blood cells from humans with potential susceptibility
Authors: Udden Mark M.
Published: October 2006

2‐Butoxyethanol causes hemolysis in rodents but not in humans. 2‐Butoxyethanol‐induced hemolysis is primarily due to the effect of its metabolite 2‐butoxyacetic acid (BAA). 2‐Butoxyacetic acid did not cause hemolytic effects when incubated with blood from a limited number of normal individuals. Because 2‐butoxyethanol is contained in many consumer products, the possibility that there may be human subpopulations susceptible to hemolysis by BAA was examined. 2‐Butoxyacetic acid was incubated with red blood cells from healthy young and older individuals and with red blood cells from patients with hereditary spherocytosis and sickle cell disease. After incubation of red blood cells with or without 2.0 mM BAA for up to 4 h, conditions that readily hemolyzed rat red blood cells, there was no increase in hemolysis or changes in mean cellular volume or morphology. The deformability of erythrocytes treated with BAA was also measured using a nuclepore filtration technique. No changes in deformability due to treatment with BAA were detected. Although BAA is a potent cause of hemolysis in rats, red blood cells in humans, including the elderly and patients with two disorders marked by chronic hemolysis, were not susceptible to BAA‐induced hemolysis or loss of deformability.
Clinical effects of organophosphorus cholinesterase inhibitors
Authors: Sidell Frederick R.
Published: October 2006

Nerve agents, highly toxic organophosphorus cholinesterase inhibitors, inhibit acetylcholinesterase and cause an accumulation of acetylcholine. Clinical effects depend on the route and amount of exposure and include miosis, bronchoconstriction, excessive secretions, vomiting, seizures, and cessation of respiratory and cardiac activity. Eye effects include miosis, engorgement of ocular vessels, pain, and a decrease in light sensitivity. Therapy consists of atropine, a cholinesterase reactivator (pralidoxime), and ventilation as needed.
Evaluation of an accelerated aging medium for acrylic bone cement based on analysis of nanoindentation measurements on laboratory‐prepared and retrieved specimens
Authors: Lewis Gladius , Xu Jie , Dunne Nicholas , Daly Catherine , Orr John
Published: October 2006

The thrust of the study was a critical evaluation of the efficacy of a medium (30% v/v H2O2, at 60°C) that has been suggested in a literature report as being suitable for simulating the oxidative aging process, seen in vivo, in the acrylic bone cement mantles of total hip and knee joint replacements. For this purpose, quasi‐static and dynamic nanoindentation measurements were used to obtain material properties—elastic modulus, E; hardness, H; and the variation of the storage and loss moduli with the frequency of the applied indenting force—of Palacos®R acrylic bone cement specimens after various periods of immersion (7, 14, 21, and 28 days) in the aging solution, and of specimens prepared from cement mantles retrieved from cemented total hip joint replacements after various times in vivo (0.92–21 years). Also, best‐fit relationships were obtained between E and time in the H2O2 solution (t), H and t, E and in vivo time (T), and H and T. This body of results points to the possibility that the aging solution is effective, although the evidence is not conclusive. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Incorporation of 2(S)‐methylbutanoic acid‐1‐14C into the structure of mevinolin
Authors: Willard Alvin K. , Smith Robert L.
Published: October 2006

A route to mevinolin () bearing (S)‐2‐methylbutanoic acid ‐1‐14C as the ester side chain has been developed. The structure of mevinolin () was degraded and selectively protected to provide the alcohol in three steps. Incorporation of 14C was accomplished by acylation of alcohol with (R,S)‐2‐methylbutyryl chloride‐1‐14C. Cleavage of the silyl ether protecting group in the resulting mixture of esters provided the two diastereoisomers and which were separated by reverse‐phase liquid chromatography. Mevinolin ‐ 14C () was also converted to the ammonium salt of the corresponding dihydroxy acid.
Deuterium labelling of the GABA agonists THIP, piperidine‐4‐sulphonic acid and the gaba uptake inhibitor THPO
Authors: Krogsgaard‐Larsen Povl , Johansen Jørgen Stage , Falch Erik
Published: October 2006

The preparations of deuterium labelled THIP ([7, 7‐2H] 4, 5, 6, 7‐tetrahydroisoxazolo [5, 4‐c]pyridin‐3‐ol) (7) and THPO ([4, 4, 7‐2H] 4, 5, 6, 7‐tetrahydroisoxazo‐lo[4, 5‐c]pyridin‐3‐ol) (14) are described. [7, 7‐2H]‐THIP (7) was synthesized by triethylamine catalyzed exchange of hydrogen for deuterium in 3‐methoxy‐6‐nitroso‐4, 5, 6, 7‐tetrahydroisoxazolo [5, 4‐c] pyridine (5) using deuterium oxide, followed by acid catalyzed denitrosation and demethylation. A similar reaction sequence was employed for the preparation of [4, 4, 7‐2H]THPO (14), though the exchange reaction on the N‐nitroso intermediate 12 required strongly basic conditions. Deuterium labelled P4S (piperidine‐4‐sulphonic acid) (17) was synthesized by catalytic deuteration of pyridine‐4‐sulphonic acid (16). The structures of the deuterated compounds 6, 7, 13, 14, and 17 were established using 1H NMR spectroscopy, in the case of 17 supported by mass spectrometry.
Marquage par 35S, 14C, 3H DE LA DI [(chloro‐2 ethyl)‐2 N‐nitroso N‐ carbamoyl], N, N‐cystamine OU cncc
Authors: Madelmont J. C. , Moreau M. F. , Parry D. , Godeneche D. , Duprat J. , Meyniel G. , Oiry J. , Imbach J. L.
Published: October 2006

Dans le but de réaliser des études de disposition et de métabolisme le CNCC a été marqué par 35S, 14C, et 3H en trois positions:

‐ on the two sulfur atom of the cystamine group

‐ on the urea carbonyl

‐ on the position 1 of the 2 chloro ethyl group.
Convenient biological preparation of pure high specific activity 14C‐labelled methane
Authors: Daniels Lacy , Zeikus J. G.
Published: October 2006

Radioactive methane of high specific activity was easily prepared using growing cultures or resuspended frozen cells of Methanobacterium thermoautotrophicum. This method gave a greater than 90% conversion of the substrate “14CO2”

No distinctions are made between CO2, HCO3 − and CO3 = when the symbol “CO2” is used.

into 14CH4 using H2 as a reductant, and is also applicable to the production of 13CH4.
Evaluation of an iodination procedure for arg8‐vasopressin
Authors: Ysewijn‐van Brussel K. A. R. N. , van Steirteghem A. C. , de Leenheer A. P.
Published: October 2006

Arg8 ‐vasopressin (AVP) was labelled with iodine‐125 using chloramine‐T. The radiochemical yield of 125I‐AVP was 71% at the specific activity (S.A.) of 784 μCi/μg AVP (29 MBq/μg AVP) as estimated by self‐displacement analysis. Immunoreactivity during storage was determined by the percent binding of 125I‐ AVP with specific antiserum. Results indicate that chloramine‐T allows high iodine incorporation with limited oxidation damage. Tracers produced were found stable for at least 5 weeks.
Synthesis of deuterium labelled eumelanin (precursor) metabolites
Authors: Pavel Stanislav , Muskiet Frits A. J.
Published: October 2006

Starting from 2,5,6‐trideutero‐3,4‐dihydroxyphenylethylamine, a mixture of 4,7‐dideutero‐5,6‐dihydroxyindole, 4,7‐dideutero‐5‐hydroxy‐6‐trideuteromethoxyindole and 4,7‐dideutero‐6‐hydroxy‐5‐trideuterometho‐ xyindole was prepared. A similar procedure for the preparation of 4,7‐dideutero‐5,6‐dihydroxyindolyl‐2‐carboxylic, 4,7‐dideutero‐5‐hydroxy‐6‐trideuteromethoxyindolyl‐2‐carboxylic and 4,7‐dideutero‐6‐hydroxy‐5‐trideuteromethoxyindolyl‐2‐carboxylic acids from methyl ester of 2,5,6‐ trideutero‐L‐3,4‐dihydroxyphenylalanine is described. The procedures are designed for the production of deuterium labelled internal standards for mass fragmentographic analysis of eumelanin (precursor) metabolites in urine. The methods can also be used for the synthesis of non‐deuterated analogs.
Synthesis of 14C‐labeled surfactants: Sodium p‐n‐dodecylbenzenesulfonate‐[phenyl‐U‐14C]
Authors: Chien David H. T. , Duncan William P.
Published: October 2006

The synthesis of sodium p‐n‐dodecylbenzenesulfonate‐[phenyl‐U‐14C], III, from benzene‐U‐14C is described. The preparative method consists of simple Friedel‐Crafts acylation, reduction of the resulting ketone, I, and sulfonation of II with chlorosulfonic acid. The specific activity of III was 6.8 mCi/mmole and the overall radiochemical yield was 25% (based on benzene‐U‐14C).
Synthesis of 14C‐hydroxyurea with immobilized 14C‐cyanate
Authors: Ajami Alfred M.
Published: October 2006

A solution of hydroxylamine hydrochloride is passed over a column bed of Amberlite IRA‐400 pre‐loaded with 14CNO− anions. 14C‐hydroxyurea is formed in 50% radiochemical yield after recrystallization. The product is not contaminated with iso‐hydroxyurea or other by‐products usually found in the reaction of hydroxylamine hydrochloride with aqueous potassium cyanate.
Preparation of tritium‐labelled jasmonic acid, ethyl dihydrojasmonate and itaconic acid
Authors: Pleiß U. , Teich A. , Stock M. , Groß D. , Schütte H. R.
Published: October 2006

A method for tritium labelling of jasmonic acid, ethyl dihydrojasmonate, and itaconic acid involving metal catalyzed hydrogen isotope exchange is described. The procedure is a convenient one‐step synthesis and specific activities in the range of 3 to 30 GBq/mmol were obtained.
Preparation of 14C‐3‐hydroxyproline from 14C‐proline by Peroxidation
Authors: Ramaswamy Sengoda G.
Published: October 2006

Conditions are described for the treatment of proline with hydrogen peroxide, ascorbic acid, and ferrous ions to produce 3‐hydroxyproline in 5–6% yield. Several reaction products are formed, but they can be separated chromatographically to yield pure trans‐3‐hydroxyproline. Synthesis of the radioactive amino acid from 14C‐L‐proline yields the pure isomer with specific activity identical to that of the starting proline. Identity of the desired product was established by chromatography, electrophoresis, and mass spectrum.
Regioselective syntheses of deuterium labelled 6‐hydroxydopamines
Authors: Simmons John , Borchardt Ronald T.
Published: October 2006

Convenient syntheses of 2,4‐,α,α‐ and β,β‐deuterium labelled 6‐hydroxydopamines have been developed. 2,4,5‐Trimethoxybenzaldehyde (1) was reductively aminated to give 2,4,5‐trimethoxybenzylamine (2). Quaternization of the amine with methyliodide followed by displacement with cyanide gave 2,4,5‐trimethoxybenzylcyanide (4). A LiAID4 reduction of 4 gave α,α‐[2H]‐β‐(2,4,5‐trimethoxyphenyl)‐ethylamine (5). Treatment of benzylcyanide 4 with n‐butyllithium/D2O gave α,α‐[2H]‐α‐cyano‐2,4,5‐trimethoxytoluene (7) which upon reduction afforded β,β‐[2H]‐β‐(2,4,5‐trimethoxyphenyl)‐ethylamine (8). Treatment of 2,4,5‐trimethoxydimethylbenzylamine 2 with n‐butyllithium/D2O gave 3,6‐[2H]‐2,4,5‐trimethoxydimethyl‐benzylamine (10). The ring deuterium atoms were retained through subsequent steps to afford β‐(3,6‐[2H]‐2,4,5‐trimethoxyphenyl)‐ethylamine (13). Removal of the phenol protecting groups afforded the deuterium labelled 2,4,5‐trihydroxyphenethylamines (6‐hydroxydopamines).