bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed neuropathy and acute toxicity studies with pirimiphos‐methyl in the hen
Authors: Lock Edward A. , Johnson Martin K. 
Published: October 2006

AbstractThis paper describes studies aimed at determining the acute anticholinergic and delayed neurotoxic potential of the organophosphate insecticide pirimiphos‐methyl (O‐2‐diethylamino‐6‐methylpyrimidin‐4‐yl O,O‐dimethyl phosphorothioate) in the hen. Delayed neuropathy was assessed by biochemical measurement of neuropathy target esterase (NTE) activities in the brain and spinal cord, clinical signs of neuropathy over two 21‐day periods and histological assessment of nervous tissue. Acetylcholinesterase (AChE) activity was also determined in the brain and spinal cord. Hens were given a single oral dose of 100 mg kg−1 pirimiphos‐methyl, which was followed by a repeated dose after 21 days. Tri‐o‐cresyl phosphate (TOCP), 500 mg kg−1, was used as a positive control. All pirimiphos‐methyl‐treated hens received prophylactic doses of N‐methylpyridinium‐2‐aldoxime methanesulphonate (P2S) and atropine sulphate.Hens dosed with pirimiphos‐methyl had very low AChE activities (<20% of control) in both the brain and spinal cord, 24 and 48 h after dosing. In the TOCP‐treated hens, the activities were about 90% of control. NTE activities in the brain and spinal cord of pirimiphos‐methyl‐treated hens were identical to those in the controls, while they were profoundly inhibited (<80%) in the TOCP‐treated hens. All hens dosed with pirimiphos‐methyl showed the expected signs of AChE inhibition and, following recovery, usually by Day 5, no clinical signs of delayed neuropathy were seen. The TOCP‐treated hens developed clinical signs of neuropathy. No histological evidence of axonal degeneration in the spinal cord or peripheral nerves was seen in pirimiphos‐methyl‐treated hens, while significant axonal degeneration occurred in the TOCP‐treated hens. Thus biochemical, clinical and neuropathological evidence indicates that pirimiphos‐methyl has no capacity, at a dose that produces severe AChE inhibition, to cause delayed neuropathy in the adult hen.
CCl4‐induced lipoperoxidation triggers a lethal defect in the liver plasma membranes
Authors: Mourelle Marisable , Meza Miguel Angel 
Published: October 2006

AbstractLoss of calcium regulation across the plasma membrane of hepatocytes is responsible for irreversible cell damage by CCl4. The mode of action of colchicine in CCl4 acute liver damage is not completely understood. We followed the time courses of the changes in lipoperoxidation, the activities of liver plasma membrane Ca2+‐ATPase, γ‐glutamyl transpeptidase and alkaline phosphatase, as well as the time courses of serum markers of liver damage in rats acutely intoxicated with CCl4. We assessed the effects of colchicine in this model and evaluated the effect of this drug on liver cytochrome P‐450. Increased lipoperoxidation is the earliest and shortest lasting effect of CCl4 in the liver and is followed by a decrease in the activities of plasma membranebound enzymes. The alterations in serum enzymes showed a slower onset and were more protracted. Colchicine pretreatment produced a small decrease in cytochrome P‐450 in the liver but completely prevented most of the changes produced by CCl4 in lipoperoxidation, liver plasma membrane enzyme activities and serum enzyme activities. We conclude that CCl4 metabolites trigger lipoperoxidation and then produce a longer lasting change in the plasma membrane, which thus allows calcium accumulation. Colchicine prevents the early mechanisms of CCl4 damage, and its effect on cytochrome P‐450 perhaps plays only a contributory role.
The short‐term effects of carcinogens and sulphur dioxide on the nuclear size of rat nasal epithelial cells
Authors: Fowlie A. J. , Grasso P. , Benford D. J. 
Published: October 2006

AbstractEnlarged nuclei have been observed frequently as an early carcinogen‐induced change in both cultured cells and in target tissues in vivo. The purpose of this work was to examine the occurrence of nuclear enlargement in the upper respiratory tract of rats to provide further evidence of whether nuclear enlargement is a reliable marker of carcinogenesis, and if it could be used as a short‐term test for respiratory carcinogens.Carcinogen‐induced nuclear enlargement is best demonstrated in vivo when/the tissue involved has been undergoing rapid replication. Male Wistar albino rats were simultaneously exposed to an atmosphere containing sulphur dioxide (which caused a hyperplastic response in the nasal cavity) and received an i.p. injection of a nitrosamine. Sections were prepared from the nasal cavity, and the nuclear areas of respiratory epithelial cells were measured. There were some increases in nuclear size 24 and 72 h after the start of treatment. The reversal of this effect 120 h after the start of treatment may have been due to the loss of the normal ciliated mucosal epithelium, and subsequent loss of metabolic capability.
Hepatic studies of intraperitoneally administered tris(2‐ethyl hexyl)trimellitate (TOTM) and di(2‐ethyl hexyl)phthalate in rats
Authors: Rathinam K. , Srivastava S. P. , Seth Prahlad K. 
Published: October 2006

AbstractAdult male rats reciving tris(2‐ethyl hexyl)trimellitate (TOTM) intraperitoneally for seven days exhibited no significant changes in the activities of hepatic aminopyrine‐N‐demethylase, aryl hydrocarbon hydroxylase or glutathione‐S‐transferase, or in the glutathione contents. However, except for the glutathkme level, the di(2‐ethyl hexyl)phthalate (DEHP)‐treated group showed significant increases in the activities of these enzymes. Changes in the body weight and the absolute and relative liver weights were also observed among the DHEP‐treated group.
Biological monitoring of workers exposed to lead stearate
Authors: Ong C. N. , Chua L. H. , Teramoto K. 
Published: October 2006

AbstractThis study was conducted to examine the usefulness of some of the commonly used biological parameters for monitoring of workers exposed to lead stearate. Forty‐two lead stearate workers from a lead stabilizer factory and 26 workers exposed to inorganic lead compounds were involved in this study. Although the workers had similar blood lead values (PbB), subjects exposed to lead stearate were found to have a significantly higher concentration of lead in plasma (PbP), (1.0 ± 0.57 μ dl−1) than workers exposed to inorganic lead compounds (0.42 ± 0.3). The ratio of PbP to PbB was ca. 2.5 times higher for lead stearate workers (0.38) than the inorganic lead workers (0.15). These data suggest that the different chemical properties of lead stearate may result in different distributional patterns of the metal in different blood components. On the other hand, the activity of δ‐aminolevulinic acid dehydratase (ALAD), an enzyme highly sensitive to lead, was not so much depressed among the lead stearate workers as that of workers handling inorganic lead. A poor correlation was also observed between PbB and ALAD activity of the stearate workers. These findings indicate that PbB and ALAD are not good biological indicators for evaluating the toxicological effect of lead stearate exposure.
1,2‐Dichloropropane hepatotoxicity in rats after inhalation exposure
Authors: di Nucci A. , Gregotti C. , Manzo L. , Imbriani M. , Ghittori S. , Bianco L. , Maestri L. , Capodaglio E. 
Published: October 2006

AbstractThe hepatic effects of 1,2‐dichloropropane (DCP) were investigated in male Wistar rats exposed to 15, 50, 100, 250, 450, 1000, 1300, 1800 or 4900 mg DCP m−3. At the end of a 4‐h period of exposure, average blood DCP levels were 0.025 and 5.38 μg ml−1 in animals treated with 15 and 1300 mg m−3, respectively. Blood DCP concentrations were correlated with the air DCP concentrations in the inhalation chamber. At DCP concentrations of 100 mg m−3 or higher, the liver non‐protein thiol (NPT) content was significantly reduced. Assays performed 20 h after 4‐h DCP exposure showed that exposure to 100–1000 mg DCP m−3 had no effect on hepatic NPT levels. The NPT content increased only in the liver of rats exposed to higher (1300–4900 mg m−3) DCP concentrations. Treatment with DCP did not cause hepatic lipid peroxidation and did not modify total protein content. The observed changes in liver cell thiol homeostasis are likely to reflect the action of reactive intermediates formed during DCP metabolism. These changes can occur in rats following exposure to considerably low levels of DCP vapour.
Variable effects of chemical allergens on serum ige concentration in mice. Preliminary evaluation of a novel approach to the identification of respiratory sensitizers
Authors: Dearman R. J. , Basketter D. A. , Kimber I. 
Published: October 2006

AbstractA wide variety of chemicals may induce allergic contact dermatitis (contact sensitivity). Some chemical allergens may, in addition, cause respiratory sensitization.Topical exposure of mice to contact and respiratory chemical sensitizers results in the initiation of divergent immune responses characteristic of preferential activation of different functional subpopulations of T helper (TH) cells. In the present study we have sought to make use of these differences, particularly differences in the ability of contact and respiratory allergens to provoke IgE responses, and to question whether opportunities exist for the identification of chemicals with the potential for respiratory sensitization. We have examined alterations in the serum concentration of IgE following topical exposure of mice to seven chemical allergens; trimellitic anhydride (TMA), phthalic anhydride, diphenylmethane‐4,4′‐diisocyanate (MDI), dicyclohexylmethane‐4,4′‐diisocyanate (HMDI), isophorone diisocyanate (IPDI), oxazolone and 2,4‐dinitrochlorobenzene (DNCB). Three of these—TMA, phthalic anhydride and MDI—are known human respiratory sensitizers. The other four—HMDI, IPDI, oxazolone and DNCB—appear not to cause respiratory allergy, or at least have a very limited potential to do so. At the concentrations tested, exposure to all chemicals caused a lymphocyte proliferative response in lymph nodes draining the site of application. However, exposure only to TMA, phthalic anhydride and MDI resulted in a substantial increase in the concentration of serum IgE. Treatment with HMDI and IPDI failed to induce any change in serum IgE concentration. DNCB and oxazolone caused only small and transient elevations of IgE that were considerably less marked than those observed with respiratory sensitizers.These data suggest that it may be possible not only to identify chemical allergens as a function of immune responses induced in mice but also to determine the form that allergic reactions may take. It is proposed that analysis of induced alterations in the serum concentration of IgE may provide a method for the identification of those chemicals that have a significant potential to cause respiratory sensitization.
Diethylbenzene inhalation‐induced electrophysiological deficits in peripheral nerves and changes in brainstem auditory evoked potentials in rats
Authors: Gagnaire F. , Becker M. N. , Marignac B. , Bonnet P. , de Ceaurriz J. 
Published: October 2006

AbstractMotor and sensory conduction velocities (MCV and SCV), amplitude of the sensory action potential (ASAP) of the tail nerve and parameters of brainstem auditory evoked potentials (BAEP) were studied in male Sprague‐Dawley rats after prolonged inhalation exposure to a commercial isomer mixture of diethylbenzene (DEB mixture) containing 6% 1, 2‐DEB. The MCV, SCV and ASAP were studied in one control group (10 rats) and three groups of 12 rats exposed to 500, 700 or 900 ppm DEB mixture for 6 h daily, 5 days per week, for 18 weeks. Rats used for recording BAEP (one control group and two other groups of 15 rats) were exposed to 600 and 800 ppm DEB mixture. The exposure time was the same.Rats exposed to DEB mixture exhibited a time‐ and concentration‐dependent decrease in MCV, SCV and ASAP and a time‐ and concentration‐dependent increase of both the peak latencies of all BAEP components and the interpeak (I–V) differences.
Alteration of brainstem auditory evoked potentials in diethylbenzene and diacetylbenzene‐treated rats
Authors: Gagnaire F. , Becker M. N. , de Ceaurriz J. 
Published: October 2006

AbstractMale Sprague‐Dawley rats were treated either with 1,2‐diethylbenzene (1,2‐DEB) or its putative active metabolite, 1,2‐diacetylbenzene (1,2‐DAB). Experimental rats and appropriate controls were examined electrophysiologically for brainstem auditory evoked potentials (BAEP). Oral administration of 1,2‐DEB (75 or 100 mg kg−1 once a day, 4 days a week, for 8 weeks) and intraperitoneal injection of 1,2‐DAB (10 or 15 mg kg−1 once a day, 4 days a week, for 8 weeks) produced time‐ and dose‐dependent increases in the peak latencies of all BAEP components as well as in interpeak (I–V) differences, and a decrease in the amplitudes of all the components. The absolute and interpeak latencies recovered partially during an 8‐week (1,2‐DEB) or a 10‐week (1,2‐DAB) recovery period, whereas there were long‐lasting decreases in peak amplitudes.
The effects of probenecid on the excretion kinetics of stanozolol, an anabolic steroid, in rats
Authors: Ryu Jae‐Chun , Kwon Oh‐Seung , Song Yun‐Seon , Yang Jong‐Soon , Park Jongsei 
Published: October 2006

AbstractThe pharmacokinetic behaviour and the mechanism of renal excretion of stanozolol (STZ), as affected by cotreatment with probenecid, were studied in male Sprague‐Dawley rats. Pharmacokinetic parameters following intravenous (i.v.) administration of STZ (20 mg kg−1 body wt.) were measured in both STZ‐treated (control) and STZ plus probenecid‐treated (treatment) groups. In order to assess the renal clearance of STZ, bolus doses of STZ and inulin (40 mg kg−1 body wt.) were injected i.v. either in the presence or absence of probenecid (40 mg kg−1 body wt.). The blood and urine concentrations of STZ were determined by capillary gas chromatography‐mass spectrometry (GC‐MS).In the probenecid treatment group, the area under the plasma disappearance and urinary excretion curves (AUC) of STZ were significantly decreased (P < 0.01) and the volume of distribution (Vd) and total clearance (CLt) were significantly increased statistically (P < 0.05 and P < 0.01, respectively). No remarkable differences in the urine flow rate, urine pH values, glomerular filtration rate (GFR) or renal clearance were observed in the treatment group. However, the clearance ratio in the treatment group was significantly increased from 11.72 to 17.27. From these results, it is suggested that the significant decrease of AUC, i.e. increase of disappearance of STZ in plasma by co‐administration with probenecid, is due to the increase of the clearance ratio.
Magnetic resonance imaging of the rat brain following acute carbon monoxide poisoning
Authors: Jalukar Vishram , Penney David G. , Crowley Michael , Simpson Nicholas 
Published: October 2006

AbstractMagnetic resonance (MR) may be used for repeatedly and non‐invasively imaging the brain. Until now, no studies have used this approach to study the effects of carbon monoxide (CO) poisoning in a defined animal model. Conscious, Levine‐prepared female rats (unilateral carotid artery and jugular vein occlusion) were exposed to 2400 ppm CO for 90 min, with or without the infusion of 50% glucose solution; CO‐stimulated increases in blood glucose and lactate occurred in both groups, while blood pressure and body temperature fell. One to four hours following termination of CO exposure, increased cortical pixel intensity, cortical surface area and brain midline shift were observed on the operated side of the brain in some rats of both groups (i.e. responders = R), providing evidence of edema. At sacrifice, 5 h following termination of CO exposure, gross water content was increased on the left side in the corresponding cortical slices in R rats, providing another measure of edema. Significant positive correlations were found between left to right pixel intensity difference and water content difference, and between the extent of midline shift and water content difference. The elevations of blood glucose and lactate concentrations, and the magnitudes of CO‐induced hypothermia and hypotension were similar to those in past studies, but appeared to exert no effect on the severity of cortical edema in terms of differences in pixel intensity, surface area, midline shift or gross tissue water content. Thus, the observed differences between the R rats and the non‐R rats is not explained by the available data. The results of this study demonstrate that MR imaging can detect changes in the cerebral cortices of rats given an acute toxic challenge with CO. Moreover, in responders the edema develops quickly, reaching nearly full development within 1 h after CO exposure.
The pattern of poisoning in urban zimbabwe
Authors: Nhachi Charles F. B. , Kasilo Ossy M. J. 
Published: October 2006

AbstractA 10‐year (1980 to 1989 inclusively) retrospective analysis of poisoning admissions to the six major referral hospitals in Zimbabwe revealed 6018 cases. The majority of the patients were aged 0–5 years (35%) and 21–30 years (22.6%). The main agents associated with acute poisoning were traditional medicines (22.9% of the total), household chemicals (18.8%, 13.2% of which was due to paraffin), snake and insect envenomation (17.1%), orthodox medicines (16.7%) and insecticides (14.8%, 10% of which is accounted for by organophosphates). Mortality was 15% and the main agents associated with fatality were pesticides, traditional medicines and orthodox medicines, in descending order. The prevention and treatment of intoxication caused by traditional and orthodox medicines, the proper storage and disposal of pesticides and legislation regulating their sale and distribution are of high priority in the fight to reduce poisoning caused by these agents.
Influence of diltiazem and/or propranolol on rat blood glucose levels in normal and diabetic animals
Authors: Salem Hatem A. , Abdel‐Rahman Mohamed S. , Dahab Gamal M. 
Published: October 2006

AbstractDiabetes mellitus and cardiovascular disorders are both common disorders, and it could be anticipated that they coexist in many patients. Diltiazem (DZ) is widely used alone or in combination with propranolol (PROP) for the treatment of hypertension and ischemic heart disease. These drugs could interfere with carbohydrate metabolism and impair glucose tolerance. The purpose of this study was to investigate the effect of oral administration of DZ, PROP (100 and 25 mg kg−1, respectively) and their combination on fasting serum glucose and insulin levels in normal and diabetic Wistar rats. Diabetes was induced by an intraperitoneal (i.p.) injection of streptozotocin (60 mg kg−1). In normal animals, serum glucose was significantly increased after DZ, PROP and DZ/PROP treatment compared to the initial values. In diabetic rats, serum glucose was significantly increased after PROP and DZ/PROP treatments, while it was slightly increased after diltiazem treatment compared to the initial values. In normal animals, plasma cAMP is significantly decreased in all treatment groups compared to the control value, while in the plasma of diabetic rats, cAMP was significantly decreased after PROP and DZ/PROP treatments when compared to the control value. Serum potassium of normal rats decreased after the diltiazem and DZ/PROP treatments, and they tend to increase slightly after PROP treatment. Serum potassium of diabetic rats was increased significantly after PROP and DZ/PROP treatments compared to the initial values. Body weight is decreased significantly in all treatment groups in normal rats while this significant decrease was observed only after DZ/PROP treatment in diabetic rats. This investigation suggests that diltiazem alone has no worsening effects on the glycemic control in diabetic rats. The hyperglycemia observed with the DZ/PROP treatment may be due to the role of PROP on increasing glucose output from the liver by cAMP.
Genetic toxicology studies with a tumor promoter
Authors: Oshiro Y. , Piper C. E. , Garriott M. L. , Balwierz P. S. , Soelter S. G. , Rohrbacher E. 
Published: October 2006

AbstractA diuretic antihypertensive agent, SC‐33643 (8‐(2‐ethoxyethyl)‐7‐phenyl‐[1,2,4]triazolo[4,3‐c]pyrimidine‐5‐amine, also known as bemitradine), was tested in the Ames test, in the mouse lymphoma TK± mutation assay, in the Chinese hamster ovary cell hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) mutation test and in the CHO chromosome aberration assay with and without metabolic activation. Additionally, the compound was tested in the rat primary hepatocyte unscheduled DNA synthesis (UDS) assay and in the mouse bone marrow micronucleus assay. The results were uniformly negative. Contrary to expectations based on the results of the battery of genetic toxicology tests, the compound produced liver, thyroid and mammary tumors in the rat (reported separately). Subsequently, SC‐36741 (5‐amino‐7‐phenyl‐[1,2,4]triazolo‐[1,5‐c] pyrimidine‐8‐ethanol, also known as desethylbemitradine), a major metabolite of SC‐33643, was tested in the Ames test, in the CHO/HGPRT mutation test and in the CHO chromosome aberration assay with and without metabolic activation, and was also tested in the rat primary hepatocyte/UDS assay and in the mouse bone marrow micronucleus assay. This metabolite also produced negative results in these tests. Therefore, SC‐33643 is a non‐genotoxic carcinogen producing tumors in rats without altering DNA or chromosomes.
Triethylbenzene‐induced sensorimotor neuropathy in rats
Authors: Gagnaire F. , Marignac B. , de Ceaurriz J. 
Published: October 2006

Abstract1,2,4‐Triethylbenzene (1,2,4‐TEB) and 1,3,5‐triethylbenzene (1,3,5‐TEB) were administered orally to male Sprague‐Dawley rats. Experimental and appropriate control rats were examined electrophysiologically for motor and sensory conduction velocities (MCV and SCV), and the amplitudes of the sensory (ASAP) and muscular action potentials (AMAP), at bi‐weekly intervals. Oral administration of 1,2,4‐TEB (200 or 400 mg kg−1, once daily, 4 days per week for 8 weeks) produced a time‐ and dose‐dependent decrease in MCV, SCV, AMAP and ASAP. Rats treated with 1,2,4‐TEB exhibited a bluish discoloration of the skin and the urine was greyish‐greenish.No changes in MCV, SCV, AMAP and ASAP developed in rats given 1,3,5‐TEB orally (200 or 400 mg kg−1, daily, 4 days per week for 8 weeks).The results indicate that 1,2,4‐TEB is a neurotoxic isomer of TEB and that the presence of two ethyl radicals in the ortho‐position on an aromatic ring could be a critical molecular arrangement resulting in chromogenic and neurotoxic properties.