bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood glutathione as a measure of exposure to toxic compounds
Authors: Simplicio P. Di , Dolara P. , Lodovici M.
Published: October 2006

Blood and liver glutathione levels were measured under the effect of an acute exposure to high doses of glutathione‐depleting substances. Among direct‐acting glutathione‐depleting substances, diethyl maleate (0.3, 0.7 and 1.4 ml kg−1) caused a marked reduction of both blood and liver glutathione, whereas methyl iodide (320 mg kg−1) led to a decrease in liver glutathione stores immediately and in blood stores with a longer latency. Indirectly glutathione‐depleting substances, like paracetamol (0.5–1.0 g kg−1) and styrene (250 mg kg−1), caused a reduction of liver glutathione, but not a similar reduction of blood glutathione. Blood glutathione is not a good measure of organ glutathione stores when dealing with indirect‐acting glutathione‐depleting substances.
Short‐term test systems to assess thiophosphoryl chloride standards
Authors: Coloşi‐Esca Doina , Anca Zoe , Barbarino Fedora , Surcel Didi , Papilian V. V.
Published: October 2006

The rat acute oral LD50 value of PSCI3 is 750 mg per kg body weight. A rat 90‐day oral feeding study at dose levels of 7.5 mg (P1) and 37.5 mg (P5) per kg resulted in increased body weight gain. Other responses inconsistently varied between dose levels. At 7.5 mg kg−1, a trend towards enhancement of relative weight of liver, spleen, kidney and adrenals was noted; at 37.5 mg kg−1, decreasing relative spleen and adrenal weights were observed. The most of the hematological and biochemical changes in blood serum cannot be believed to be transitory adaptive changes, but valid toxic effects. On the other hand, there are some indicators that suggest a possible trophic effect of this compound. However, the reversible dystrophic changes in liver, as well as the histochemical and histoenzymical results, require us to take into account that inactive chronic hepatitis could be reactivated by further toxic insult. A teratology study demonstrated increased number, body weight and length of fetuses, without apparent pathological events (tumors, external malformations). A mutagenicity test performed on rat femoral bone marrow after 30‐days feeding of 37.5 mg kg−1 did not indicate any significant change in the incidence of chromosomal aberrations, compared with the control group. The recommended maximum allowable concentration in the working zone for thiophosphoryl chloride in air was set at 3 mg m−3.
Gamma‐glutamyl transpeptidase: A sensitive marker in DDT and toxaphene exposure
Authors: García B. Martha , Mourelle Marisabel
Published: October 2006

Gamma‐glutamyl transpeptidase (GGTP) activity in rat liver plasma membrane and blood serum was investigated as an analytical marker for studying acute and sub‐chronic exposure to DDT and toxaphene. Twenty‐four hours after a single oral dose of DDT (200 mg per kg body weight) or toxaphene (110 mg per kg body weight), GGTP activity increased two‐fold in liver plasma membranes, followed by a return to normal values 48 h post‐exposure. In addition, serum GGTP activity doubled following acute exposure to DDT or toxaphene, and remained elevated for 48 and 96 h, respectively. Following 2 months continuous exposure to either insecticide, serum GGTP activity levels increased to double that of control values. GGTP activity in liver plasma membranes was elevated 2.5‐fold following the initial treatment with toxaphene (16.5 mg per kg body weight per day) and the activity remained high throughout the treatment period (120 days). Prolonged exposure with DDT (30 mg per kg body weight per day) did not produce any change in liver GGTP activity. Based on these results, it appears that GGTP activity could be used as a marker for acute DDT and toxaphene exposure.
Acute target organ toxicity of 1‐nitronaphthalene in the rat
Authors: Johnson Dale E. , Riley Michael G. I. , Cornish Herbert H.
Published: October 2006

1‐Nitronaphthalene (1‐NN) produced respiratory distress and centrilobular liver necrosis in male Sprague‐Dawley rats after a single intraperitoneal injection (100 mg kg−1). Microscopic examination of the lungs of rats killed 24 h after the injection revealed a highly selective non‐ciliated bronchiolar (Clara) cell necrosis as the only remarkable lesion. Pretreatment of animals with phenobarbital offered complete protection from the respiratory distress induced by 1‐NN, but increased the severity of the hepatotoxicity. Pretreatment with SKF‐525A protected against 1‐NN‐induced liver necrosis, but did not alter the incidence or severity of the respiratory distress. Under similar conditions, this pattern of toxicity was not seen with the structural analogue 2‐nitronaphthalene.
Comparative effects of various lead salts on delayed hypersensitivity in mice
Authors: Descotes Jacques , Evreux Jean Claude , Laschi‐Locquerie Alda , Tachon Pierre
Published: October 2006

Intraperitoneal administration of lead acetate, lead carbonate, lead chloride, lead nitrate or lead oxide at 0.5 or 6 mg per kg per day on five consecutive days was found to produce diverging effects on delayed hypersensitivity to sheep erythrocytes in Balb/c mice according to the salt used. Lead carbonate, lead nitrate and lead oxide exerted immunosuppressing properties, while lead acetate and lead chloride enhanced this cell‐mediated immune response. From these findings, it is concluded that lead immunotoxicity critically depends on which salt is present.
Dimethylnitrosamine genotoxicity in rat liver primary cell cultures with low cytochrome P‐450 levels
Authors: Mendoza‐Figueroa Tomäs
Published: October 2006

Liver primary cell cultures (LPCC) with decreasing concentrations of cytochrome P‐450 were used to investigate the genotoxicity of the hepatic carcinogen dimethylnitrosamine (DMN) and the correlation between DMN genotoxicity and cytochrome P‐450 levels. Hepatocytes were isolated from partially hepatectomized rats and incubated with [3H]thymidine; single‐strand DNA molecular weight was determined by alkaline sucrose sedimentation. The molecular weight of DNA decreased 50% in LPCC plated either 2 or 24 h before being treated for 24 h with 70 μm DMN. Cytochrome P‐450 content was 188 pmol per mg protein in freshly isolated hepatocytes, whereas it was 70 and 32 pmol per mg protein in hepatocytes that had been cultured 24 and 48 h, respectively. Incorporation of 14C into acid‐insoluble material was the same in LPCC exposed 24 h to [14C]DMN starting either 2 or 24 h after cell plating. At non‐toxic concentrations (0.01‐1 μM), SKF 525‐A, an inhibitor of mixed‐function oxidase enzymes, inhibited approximately 20% of the binding of 14C from [14C]DMN to acid‐insoluble material in LPCC plated either 2 or 24 h before they were exposed to DMN for 24 h. Hepatocyte cultures exposed to the direct‐acting alkylating agent N‐methyl‐N‐nitro‐N‐nitrosoguanidine (at concentrations ranging between 6.8 × 10−8 and 6.8 × 10−5M) starting 2 and 24 h after plating, exhibited significant unscheduled DNA synthesis. These results indicate that DMN genotoxicity was similar in LPCC differing considerably in cytochrome P‐450 levels, and they suggest that DMN genotoxicity in these cultures is due mainly to similar DMN activation than to decreased DNA repair.
The effect of substrate and potassium on the inhibitory kinetics of mnci2 on the enzyme k+‐p‐nitrophenyl phosphatase in rat brain
Authors: Bansal S. K. , Husain Tahir , Murthy R. C. , Chandra S. V.
Published: October 2006

The effect of Mn2+, a divalent metal, on the enzyme K+‐p‐nitrophenyl phosphatase (K+‐PNPPase) was studied in rat brain. The metal was found to be a moderate inhibitor of the enzyme, with an I50 of approximately 480 μM. The inhibition was pH dependent, but not temperature dependent. On measurement of the inhibition with varying concentrations of PNPP (1–5 mM), the I50 value remained constant. However, when the inhibition was measured with K+ (5–20 mM), the lso value increased from 130 μM to 490 μM, suggesting that K+ antagonized the effect of Mn2+. In kinetic studies, Mn2+ inhibited the enzyme in a non‐competitive manner with respect to PNPP. The Km remained constant (2.9), but the Fmax was decreased from 5.0 to 1.6. However, with respect to K+, the inhibition was competitive, as the concentration for half maximal activation (K0.5) increased from 1.3 to 8.9 mmol I−1 with 1 mM of MnCl2, suggesting that the apparent affinity of K+ for the enzyme was decreased. The apparent Vmax was not affected. The degree of cooperativity (n) measured as the slope of the Hill plot remained unaltered (1.9 ± 0.2) over the entire concentration range of MnCl2 tested.
Application of dimethyl sulfoxide to skin of white and hairless mice
Authors: McGraw J. Leon , Greco John
Published: October 2006

Dimethyl sulfoxide (DMSO) was applied to a 2‐cm2 area on the backs of four groups of mice for a 5‐min period each day, 5 days per week, for the designated periods: groups I and II — six hairless albino mice (hrhr, c/c) per group — were treated for 8 weeks; group III — three hairless albino mice (hrhr, c/c) — were treated for 4 weeks; group IV — three white mice (ICR Swiss) — were treated for 8 weeks. A group of six untreated hairless albino mice (hrhr, c/c) (group V) functioned as controls for groups I, II and III, and a group of three white mice (ICR Swiss) (group VI) served as controls for group IV. Except for DMSO applications, controls were handled and treated in the same way as the experimental groups. At the end of the experimental periods, the claws of all appendages were removed, measured and average lengths were determined. The claws of group I and group II hairless albino mice were, on average, 2.4‐fold longer than the claws of the control hairless albino mice, a significant increase (p<0.01) in the average claw length. There was no significant difference in the lengths of the claws of the group III mice after 4 weeks of DMSO application. The claws of group IV (ICR Swiss mice) were, on average, 1.2‐fold longer than the claws of the control white mice, representing a significant increase (p <0.02) in claw length after 8 weeks of DMSO application.
Studies on the mechanism of toxicity of the mycotoxin sporidesmin. IV. Inhibition by copper‐chelating agents of the generation of superoxide radical by sporidesmin
Authors: Munday K.
Published: October 2006

Sporidesmin, the mycotoxin responsible for “facial eczema” in ruminants, has previously been shown to generate superoxide free radical, the latter being formed during autoxidation of the reduced form of the mycotoxin, a dithiol. The autoxidation of reduced sporidesmin is catalysed by iron and by copper, although cobalt, nickel, manganese, cerium, vanadium and molybdenum were found to be without effect. The catalytic activity of copper was some 900‐fold that of iron. Cyanide and certain organic complexing agents inhibit superoxide production from reduced sporidesmin by virtue of their ability to chelate copper. Some proteins behave likewise, again through binding of the metal catalyst, although arnino acid‐bound copper was found to be as effective as ionic copper in catalysing the autoxidation reaction. From the results of the present experiments, it is suggested that any superoxide production from sporidesmin in vivo would be mediated by the intracellular transport pool of copper. Furthermore, the ability of zinc to inhibit intestinal absorption of copper may be involved in the mechanism whereby salts of this metal afford protection against the harmful effects of sporidesmin in the living animal.
Renal handling of ‘filterable’ plasma metals and organic substances in man
Authors: Yokoyama Kazuhito , Araki Shunichi , Yamamoto Reiko
Published: October 2006

To estimate the plasma ‘filterable’ form concentration, glomerular filtration and tubular reabsorption in man for metals and organic substances, the regressions of the 24‐h urinary excretion of lead (Pb), inorganic mercury (Hg), δ‐aminolevulinic acid (ALA) and coproporphyrinogen (CP‐gen) on glomerular filtration rate were examined. The regressions were significant for ALA in two ‘healthy’ men examined and for Pb and for CP‐gen in one of them. From these data, it was estimated that the plasma concentration of ‘filterable’Pb was approximately 0.01 μg dl−1; the ALA concentration was 2.3 and 4.5 μg dl−1; and CP‐gen was 0.11 μg dl−1. Similarly, the filtered loads of Pb, ALA and CP‐gen were assumed to be nearly twice as large as their urinary excretion. Hg was not considered to undergo glomerular filtration.
Teratologic evaluation of alcide® liquid in rats and mice. I
Authors: Skowronski Gloria A. , Abdel‐Rahman Mohamed S. , Gerges Samy E. , Klein Kenneth M.
Published: October 2006

Alcide®, a liquid sterilizer, was evaluated for teratogenic potential in rats and mice. Sodium chlorite and lactic acid, the active ingredients of this compound, form chlorine dioxide when mixed. Pregnant rats and mice were administered 1 ml and 0.1 ml, respectively, of Alcide® liquid by gavage on days 6–15 of gestation. The general health of the dams was evaluated and the fetuses examined for external, visceral and skeletal malformations. There was no evidence of maternal toxicity among treated rats and mice. Fetal viability, weight, length and number of resorptions were comparable with control groups. Teratogenic toxicity was not detected in either species. There was some incidence of skeletal and visceral anomalies; however, these variances were not significantly different from control animals.
Respiration of F344 rats in nose‐only inhalation exposure tubes
Authors: Mauderly Joe L.
Published: October 2006

The respiration of naive F344 rats confined in nose‐only inhalation exposure tubes was measured to obtain data for normal adult rats of different ages and to evaluate the tubes for exposures lasting several hours. Exposure tubes were modified for use as volume‐displacement plethysmographs. Respiration of 10 male and 10 female rats at 3, 6, 12 and 24 months of age was measured in the tubes during simulated exposures of up to 6 h duration. Measurements included respiratory frequency, tidal volume, minute volume and body surface temperature. The mean respiratory frequencies of 3, 6, 12 and 24 month old rats during the first hour of exposure were 172, 152, 123 and 136 breaths min−1, respectively. Minute volumes were 1.40, 089, 0.67 and 0.82 ml g−1 body weight, respectively. Both frequency and minute volume g−1 body weight were significantly greater for the youngest group, declined with age to 12 months and then increased at 24 months. Minute volumes g−1 body weight were similar for males and females. Minute volume and respiratory frequency of 3 and 12 month old rats declined progressively between 1 and 6 h of confinement in the tubes. Surface temperature did not increase after the first hour. The age and sex‐specific data provide a basis for predicting respiration of naive tube‐confined rats during inhalation exposures to non‐irritating materials.
Intestinal absorption of aluminum in rats: Effect of intraluminal pH and aluminum concentration
Authors: van der Voet Gijsbert B. , de Wolff Frederik A.
Published: October 2006

The intestinal absorption of aluminum (Al) was studied in an in situ perfusion system of rat small intestine in combination with systemic and portal blood sampling. The jejunum‐ileum was perfused with media containing 4.63, 9.25 and 18.50 mmol l−1 Al chloride at pH 4.0 and 7.0. Both mucosal retention and release of Al into the blood increased at increasing perfusate concentrations. Mucosal retention was not affected by pH but at lower pH more Al was released into the blood. The amount of Al which appeared in the blood was linearly related to the mucosal retention. The Al release into the blood was much less (μmol l−1) than the mucosal retention (mmol l−1). It is concluded that the intestinal absorption of Al is pH‐ and concentration‐dependent.
The role of the red blood cell in the transport of carbon disulfide
Authors: Lam Chiu‐Wing , Distefano Victor , Morken Donald A.
Published: October 2006

When rats were exposed to 2 mg l−1 (˜640 ppm) of carbon dislfide (CS2) for 4 h, the concentration of free CS2 in the red blood cells (RBCs) approached a plateau within 2 h. Free CS2 in plasma reached a steady state concentration within 15 min of exposure. More than 90% of the free CS2 in blood was found in the RBCs regardless of the length of exposure. In vitro studies showed that about 90% of the free CS2 partitioned into the RBCs regardless of whether the CS2 was added first to the plasma or directly to the RBCs. Hence, it appears that the RBC is the major carrier of CS2 in blood. It was found that 98% of the free CS2 in red blood cell lysates was associated with hemoglobin. Free CS2 in RBCs was readily partitioned into olive oil (RBCs/oil=1/6), less readily into the plasma (RBCs/plsma=12/1), and only to a small extent into phosphate buffer (RBCs/buffer=39/1). The extraction of free CS2‐loaded RBCs into albumin solution increased with increasing albumin concentrations. CS2 can be extracted with buffer, protein solution, and oil, indicating that CS2 in RBCs can be transferred to the medium in which the RBCs contact. It is proposed that RBCs may also play an important role in the transport of CS2 from lung to tissues and vice versa. The possible role of RBCs in the transport of other organic solvents in the blood is also discussed.
Detection of andromedotoxins for the diagnosis of rhododendron poisoning in animals
Authors: Humphreys D. J. , Stodulski J. B. J.
Published: October 2006

A method for the detection of andromedotoxin in plant material and relicta from cases of poisoning due to Rhododendron and other members of the Ericacea is described. This method, which overcomes the problems associated with basing the diagnosis on the clinical signs exhibited and untrained identification of plant materials, has been successfully applied to the investigation of a number of field outbreaks of Rhododendron poisoning in animals.
Penetration of nicotine and nitrosonornicotine across porcine oral mucosa
Authors: Squier C. A.
Published: October 2006

The use of smokeless tobacco (chewing tobacco or snuff) results in contact between this material and the lining of the mouth over relatively long periods of time. As tobacco contains nicotine and a carcinogen, nitrosonornicotine (NNN) there is a likelihood of systemic absorption of both these compounds under these conditions. This study measured the penetration of nicotine and NNN across skin and various regions of oral mucosa. Specimens of porcine skin, keratinized gingiva and non‐keratinized floor of mouth and cheek mucosa were placed in perfusion chambers and the flux across these tissues of isotopically labeled water, nicotine and NNN was determined; permeability constants were calculated for each compound and for each region and the values compared statistically. Skin showed a lower permeability than the oral regions to all compounds and floor of mouth was generally the most permeable site. Nicotine passed across oral mucosa almost as rapidly as water, the most permeable region being floor of mouth, whereas gingiva and buccal mucosa showed a similar, but lower, permeability. The non‐keratinized oral carcinomas, regions with the higher permeability being sites that show the greatest tendency to develop such lesions.
Reproductive toxicology of inhaled styrene oxide in rats and rabbits
Authors: Sikov Melvin R. , Cannon William C. , Carr Daniel B. , Miller Rodney A. , Niemeier Richard W. , Hardin Bryan D.
Published: October 2006

Experiments were performed to evalute reproductive and developmental toxicology in rats and rabbits exposed to styrene oxide by inhalation. Female rats were exposed to 100 or 300 ppm styrene oxide or to filtered air for 7 h/day, 5 days/week for 3 weeks. Extensive mortality occurred in rats that received prolonged exposure to 100 ppm styrene oxide while 300 ppm was rapidly lethal. As a result exposures were terminated in this latter group and the group was eliminated from further study. The rats of the 0 and 100 ppm groups were then mated and exposed to 0 or 100 ppm styrene oxide daily through 18 days of gestation (dg).

Female rabbits were artificially inseminated and exposed for 7 h daily to 0, 15, or 50 ppm styrene oxide through 24 dg. Both of these lower concentrations used for exposure of the rabbits produced mortality of does. The rats were killed at 20 dg and the rabbits at 30 dg. Pregnant animals were examined for toxic changes including altered tissue weights and histopathologic effects. Litters were evaluated using several measures of embryotoxicity, and live fetuses were examined for external, visceral, and skeletal malformations.

Exposure during gestatation appeared to increase preimplantation loss in rats, and tended to increase the incidence of resorptions in rabbits. In both species, fetal weights and crown‐rump lengths were reduced by gestational exposure. The incidences of ossification defects of the sternebrae aned occipital bones were increased by gestational exposure of rats to styrene oxide. These results indicate that inhalation exposures at these concentrations produce reproductive and development toxicity, as well as maternal toxicity.
The teratogenic potential and dose–response of dermally administered ethylene glycol monomethyl ether (EGME) estimated in rats with the chernoff–kavlock assay
Authors: Wickramaratne G. A. De S.
Published: October 2006

The Chernoff and Kavlock in vivo assay was used to study the teratogenic potential of ethylene glycol monomethyl ether (EGME). It was administered to pregnant rats on days 6–17 (inclusive) of gestation by the dermal route at an application rate of 10 ml kg−1 body weight of 3%, 10%, 30% and 100% EGME with physiological saline as the solvent. 100% was lethal to the pregnant rats, 30% was lethal to the fetuses, 10% produced small litter sizes with poor survival and 3% had no adverse effects. By the ‘rules’ developed to evaluate results from the assay, 10% was judged to be a potentially teratogenic dose in the rats. The study also demonstrated the usefulness of this assay for pre‐screening or additional investigations for suspected teratogens when route of exposure could be important in determining the potential hazard.
Determination of rat β2‐microglobulin in urine and in serum. I. development of an immunoassay based on latex particles agglutination
Authors: Viau C. , Bernard A. , Lauwerys R.
Published: October 2006

Rat β2‐microglobulin has been isolated from the urine of rats pretreated with sodium chromate. The purified protein was used to raise antisera in two rabbits. Treatment of the antisera with ammonium sulphate followed by gel chromatography led to an immunoglobulin fraction which was used to coat latex particles by physical adsorption. The latex suspension was used in an automated system including an optical particle counter to analyse the protein in serum, urine and cerebrospinal fluid. Serum contains 5.8 mg of β2‐microglobulin/l, of which 33% is found as a 55000 dalton complex while 66% is present as the ‘free’ protein. The daily urinary excretion of β2‐microglobulin in females is about 2 μg of which 7% is found to be a 65000‐dalton complex while 92% is the free protein. From this, it can be calculated that the fractional urinary excretion of β2‐microglobulin is about 0.03%. The cerebrospinal fluid contains about 1 mg of β2‐microglobulin/l. Preliminary tests also suggest that the method can be adapted for non‐automated turbidimetric detection. In the automated assay, the within‐ and between‐assay coefficients of variation are less than 10% for the three biological fluids tested. The analytical recovery in the urine is 93%. In urine, β2‐microglobulin undergoes proteolytic degradation at pH below 6. This does not represent a serious drawback to its use as a sensitive index of tubular function since in most experimental circumstances, rats excrete urine with a pH above this value.
Comparison of the effects of urinary flow on adjusted and non‐adjusted excretion of heavy metals and organic substances in ‘healthy’ men
Authors: Araki S. , Murata K. , Aono H. , Yanagihara S. , Niinuma Y. , Yamamoto R. , Ishihara N.
Published: October 2006

The effect of variation in urinary flow rate (ml urine min−1, UF) on adjusted and non‐adjusted urinary excretion of metals and organic substances was examined in ten ‘healthy’ men. The effect of UF was found to be eliminated when urinary concentrations of lead (Pb), hippuric acid (HA), delta‐aminolevulinic acid (ALA) and coproporphyrin (CP) were adjusted to urinary specific gravity and to UF. Similarly, the effect of UF on inorganic mercury (Hg) was eliminated when the concentration was adjusted to timed excretion and to UF. The effect on zinc (Zn) and copper (Cu) was eliminated when adjusted to urinary creatinine (Cn) and to UF. The difference in the effect of UF on the adjusted urinary excretion was explained by the effect of UF on timed excretion of substance, which was ranked in the following order: Pb, HA, total urinary solutes, ALA and CP; Zn; Cu; Cn; and Hg. It was concluded that ‘UF‐adjusted concentration’ is applicable to measurement of all substances in urine as a method of minimizing UF effects, while the other three adjustment methods have only limited uses.
Chelation in metal intoxication. XIX. α‐mercapto‐β‐aryl acrylic acid as antidotes to nickel and lead toxicity
Authors: Sharma B. L. , Kachru D. N. , Singh S. , Tandon S. K.
Published: October 2006

In view of the reported effectiveness of α‐mercapto‐β‐(2‐furyl) acrylic acid (MFA) as an effective antidote to inorganic mercury toxicity, some α‐mercapto‐β‐aryl acrylic acids were synthesized and examined for their efficacy in counteracting nickel and lead intoxication in rats. α‐mercapto‐β‐(3,4‐dimethoxyphenyl)acrylic acid (MDA) was most effective and other compounds were less but about equally effective in enhancing urinary excretion and in reducing tissue concentration of Ni. MDA was the only compound to remove Ni from the brain. MFA was also more effective than other structurally related compounds in enhancing urinary and faecal excretion and in lowering body burden of Pb. All the compounds significantly reduced the inhibition of the activity of blood δ‐aminolevulinic acid dehydratase (δ‐ALA‐D) and increase in the urinary excretion of δ‐aminolevulinic acid (δ‐ALA) caused by Pb. The results do not show any relationship between the nature of the substitution at the β‐position of α‐mercapto acrylic acids and their ability to reduce the concentration and the toxic effects of the two metals. However, these thiol chelating agents appear promising as antidotes to Ni and Pb poisoning.
Cyanide stimulation of tri‐N‐butyltin mediated hemolysis
Authors: Gray Brian H. , Porvaznik Martin , Lee Lanfong H.
Published: October 2006

The effects of tributyltin and sodium cyanide on hemolysis in human erythrocytes are described. Tributyltin has a sharp cut‐off concentration for induction of hemolysis. A 5 μM concentration of tributyltin induces hemolysis and 1 μM or less does not in erythrocyte supensions with 2.3×108 cells per ml. The kinetics for tributyltin‐induced hemolysis are sigmoidal indicating a complex molecular mechanism leading to lysis. Ten mM sodium cyanide plus 1 μM tributyltin does not stimulate hemolysis rates above levels observed with 10 mM sodium cyanide alone. Five mM sodium cyanide plus hemolytic concentrations of tributyltin stimulates hemolysis rates synergistically compared with either cyanide or tributyltin alone. Ultrastructurally, hemolytic concentrations of tributyltin can be visualized in the electron microscope by osmium staining during fixation as electron‐dense spheres penetrating the lipid bilayer of the erythrocyte plasma membrane. Ten mM sodium cyanide plus 25 μM tributyltin increases slightly the size of osmiophilic structures in erythrocyte membranes compared with those spheres seen in cells exposed to 25 μM tributyltin alone. Sodium cyanide is the only compound tested that stimulates tributyltin‐induced hemolysis. Sodium thiocynate, previously shown to be rapidly exchanged across erythrocyte membranes by tributyltin, reduces the rate of hemolysis. It is likely that sodium cyanide stimulates hemolysis in the presence of hemolytic tributyltin concentrations because the multimolecular, membrane‐intercalated, tributytin aggregates are transporting cyanide anion by the electrically silent, anion exchange mechanism demonstrated for other anions. It is suggested that this mechanism delivers cyanide anion to or near critical membrane sites where it is available for enzyme inhibition or cross‐linking of protein sulfhydryl groups.
Stimulation of lipid peroxidation and impairment of glutathione‐dependent defence system in the liver of rats repeatedly treated with carbon tetrachloride
Authors: Yalçin A. Süha , Koçak‐Toker Necla , Uysal Müjdat , Aykaç Gülçin , Sivas Ahmet , Öz Hikmet
Published: October 2006

To study the effect of carbon tetrachloride treatment on hepatic lipid peroxidation and glutathione‐dependent defence system, rats were injected with carbon tetrachloride (0.2 ml/kg body weight, i.p.) twice weekly for a period of 4 weeks. Carbon tetrachloride treatment caused a significant increase in hepatic lipid peroxide levels and significant decreases in hepatic glutathione levels and glutathione peroxidase and glutathione transferase activities. These results show that chronic carbon tetrachloride administration to rats leads to the stimulation of hepatic lipid peroxidation, which seems to be the consequence of impaired cellular defence by glutathione and glutathione‐related enzymes.
Effects of diflubenzuron on the mouse liver
Authors: Young Mark F. , Trombetta Louis D. , Carson Steven
Published: October 2006

Diflubenzuron (DFB), a potent inhibitor of insect chitin synthesis, was administered to Swiss Webster mice in a 30‐day oral intubation study. Animal groups received either no treatment, vehicle control (Polyehylene glycol 400), or DFB suspensions at doses of 125, 500, and 2000 mg/kg body weight. Hepatic gluta thione S‐transferase activity as well as morphological characteristics were studied. DFB was shownn to elicit hepatocellular changes at all dose levels. The activities of three glutathione S‐transferases (S‐aryl, S‐aralkyl, and S‐epoxide) were all altered after DFB administration. Light microscopy revealed radial arrays of hepatocellular vacuolization between the portal and central vein areas. Electron‐microscopic examination, verified by morphometric analysis, revealed degenerativ changes as well as an increased volume density of the endoplasmic reticulum.
Teratologic studies on alcide Allay® gel in rabbits
Authors: Abdel‐Rahman Mohamed S. , Skowronski Gloria A. , Gerges Samy E. , von Hagen Stanley , Turkall Rita M.
Published: October 2006

Alcide Allay® gel, a highly effective germicidal compound, was evaluated for teratogenic potential in rabbits. Pregnant rabbits were administered 2 g/kg Allay® get (containing either of two concentrations of sodium chlorite as active ingredient) or placebo topically on days 6–18 of gestation. Moderate to severe erythema was recorded in the high‐dose gel group on day 11 (Draize score = 3.5). By day 18, the skin of all rabbits in the high dose treatment group appeared normal. Decreased maternal body weight gain was observed in the low dose and placebo gel groups. Fetal weights and lengths were significantly reduced in all gel groups. There was some incidence of skeletal anomalies in all gel treated groups, however, these incidences were not statistically different from the control group. The commonly occurring skeletal defects were incomplete ossification of skull bones, small or missing sternebrae, and extra ribs. The incidence of visceral abnormalities in all gel groups was not statistically different from control animals. Visceral anomalies included heart displacement, fusion or serration of the liver, and kidney displacement. Alcide Allay® gel at 2 g/kg was non‐teratogenic to rabbit fetuses.
Pithomyces chartarum spore counts in rumen contents and faeces of sheep exposed to autumn pasture at three different grazing pressures
Authors: Smith B. L. , Embling P. P. , Gravett I. M.
Published: October 2006

Three groups, each of 18 lambs were grazed during autumn in paddocks which had been divided longitudinally by temporary fencing to give twofold differences in grazing intensity between the groups. During the period when spore numbers were elevated the high grazing pressure (HGP) group lost some body weight (−34 g/day). The low grazing pressure (LGP) group gained +90 g/day and the intermediate grazing pressure (IGP) group gained weight slightly (+14 g/day). There were two spore rises during the experimental grazing period, a minor and a major rise. Peak pasture spore counts were 88 000, 130 000 and 282 000 spores/g grass for the LGP, IGP and HGP groups respectively. These were reflected in the peak rumen content counts which were 6640, 17 050 and 24 470 spores/g and the faecal peak counts which were 141 400, 330 800 and 568 200 spores/g for the LGP, IGP and HGP groups respectively. Liver injury scores were 0.9, 2.6 and 1.7 and peak mean serum GGT levels were 139, 312 and 220 U/I for the LGP, IGP and HGP groups respectively. The greater liver injury in the IGP groups was considered due to the greater total consumption of spores caused by the combination of pasture spore concentration and dry matter intake.
Aluminium induced damage of the lysosomes in the liver, spleen and kidneys of rats
Authors: Stein Günter , Laske Volker , Müller Andreas , Bräunlich Helmut , Linß Werner , Fleck Christian
Published: October 2006

The influence of repeated aluminium (Al) administration (0.05 or 0.5 mg 100 g−1 b.w.t. i.p. 5 times weekly for 12 weeks) on the lysosomal enzymes N‐acetyl‐beta‐D‐glucosaminidase (β‐NAG) and beta‐glucuronidase (β‐Gluc) in serum, liver, spleen and kidneys of adult female rats with intact kidneys, (NR), or following partial nephrectomy (5/6 NX) was investigated. After Al loading, at the high dose only, the β‐NAG in serum and the free β‐NAG in liver, spleen and kidneys increased. Latent β‐NAG levels decreased in all three organs the effect being dose related. Following Al loading no elevation in total enzyme activity was observed, with one exception. Depending on Al doses the spleen of the non‐operated animals, the liver of both groups of animals and the serum showed a decrease in β‐Gluc activity. No effect on β‐Gluc activity was observed in the spleen of 5/6 NX animals or in the kidneys of either group of animals. The results confirm that high doses of Al induce toxic effects and damage the lysosomes in the liver, the spleen and the kidneys. The results indicate that the extent of lysosomal damage correlates with dose and duration of Al loading. Repeated administration of Al also interferes selectively with enzyme synthesis.
A programmed feedback control of solvent vapour concentrations in experimental inhalation chambers
Authors: Bonnet P. , Raoult G. , Delcourt J. , Jeandel B. , de Ceaurriz J.
Published: October 2006

This paper describes a computer‐controlled system to regulate solvent vapour concentrations in experimental inhalation devices. This system consists of an exposure chamber, a bubbler with a mass flow‐meter, a monitor gas chromatograph and a computer. The frequency of automatic sampling was dependent upon the retention time of test materials. Flow‐rate was corrected through a computer regulated bubbler as soon as the mean chamber concentration varied by more tham 2.5% of a command level. Regulation coefficients were calculated by relating the concentration of vapours sampled with adsorbent tubes to the mean peak areas given by the mantor gas chromatograph. They were then fed into the computer allowing the actual concentration to be adjusted to the command level. Deliberately induced fluctuations in the level of acetone, ethanol and trichloroethylene, either sudden or progressive, were satisfactorily corrected as were fluctuations occurring normally during repeated exposures to ethanol. Variations were generally inferior to 5% of the command level.
Renal and hepatic lesions induced by 2,2,4‐trimethylpentane
Authors: Fowlie A. J. , Grasso P. , Bridges J. W.
Published: October 2006

The renal changes produced by 2,2,4‐trimethylpentane, a constituent of unleaded gasoline, are studied in Wistar rats. The compound was given at a dose of 2 ml/kg daily by gavage dissolved in corn oil (2:1) to nine Wistar Albino rats. Nine control male rats received an equivalent dose of corn oil. Six animals were housed in metabowls to allow the collection of urine for enzyme and urinanalysis. The remaining three animals of each group were housed in a normal animal cage. After 2 days of treatment, all the test rats were noted to have lost weight and were killed on this or on the subsequent day. Macroscopic examination of the livers and kidneys revealed no visible lesions on the kidney, but two of the rats had white, slightly raised patches on the liver. Microscopic examination demonstrated centrilobular and confluent necrosis, hydropic degeneration and vaculolation of hepatocytes. Microscopic examination of the kidneys indicated eosinophilic hyaline droplet accumulation in the cells of the tubules, and tubular dilation. Analysis of plasma alkaline phosphatase and aspartate transominase activity revealed increases consistent with liver damage. Analysis of urinary N‐acetyl‐β‐glucosaminidase and alkaline phosphatase activity showed increases consistent with renal toxicity. An apparent increase in the amount of cellular debris in the urine was also found, when the sediment was examined microscopically.

From this study, it would appear that 2,2,4‐trimethylpentane possess hepatotoxic as well as nephrotoxic properties.
Aspirin disposition in rats acutely intoxicated with CCl4
Authors: Favari Liliana , Mourelle Marisabel , Amezcua Joseg Luis
Published: October 2006

The profile of urinary salicylate metabolites was determined after an oral administration of acetylsalicylic acid (ASA) to: 1, control rats; 2, rats treated with CCl4 and 3, rats intoxicated with CCl4 and also pretreated with colchicine for 7 days. The following enzymatic activities were determined: liver and plasma ASA‐esterase, liver UDP‐glucuronyltransferase and liver aniline hydroxylase. The time course of plasma concentration of salicylates in similar groups were followed after the intraperitoneal administration of acetylsalicylic acid (ASA), salicylic acid (SA) or gentisic acid (GA). The animals acutely intoxicated with CCl4 showed a reduction in urinary excretion of glucuronates and an increased urinary excretion of gentisic and salicylic acids. The activities of plasma and liver ASA‐esterases were significantly increased in CCl4‐treated rats while the aniline hydroxylase was reduced and the UDP‐glucuronyltransferase remained unchanged. The plasma half lives of salicylates were reduced in CCl4‐treated rats regardless of the administered parent compound. Colchicine pre‐treatment completely prevented the alterations produced by acute intoxication with CCl4. The heterogeneity of liver metabolic disfunctions present in acute liver damage was evidenced. It is emphasized that the pharmacokinetic alterations produced by acute liver injury can be the result of complex factors that may involve changes in circulation, hepatic binding protein and other routes of elimination.
Haemotoxicity to chicken (Gallus gallus domesticus) by technical and formulation grades of some phosphoric and synthetic pyrethroid esters
Authors: Qadri Syed S. H. , Jabeen K. , Mahboob M. , Mustafa M.
Published: October 2006

Acute toxicity was studied by administering an encapsulated single dose to chickens (G.g. domesticus) and observing them for 21 days. Azodrin‐71 (Tech.) was found to be extremely toxic, whereas Cypermethrin‐92 (Tech.), Cypermethrin‐25 EC and Permasect‐25 EC (Form.) were practically non‐toxic based on LD50 value determinations.

Sub‐acute oral haemotoxicity of technical and formulation grades of these insecticides was also studied by administering encapsulated low, medium and high daily doses for 21 days to chickens and recording clinical symptoms, mortality and haematological parameters pre and post‐dosing.

Clinically high doses of Azodrin‐71 (Tech.) caused tremors and ataxia among chicks on the 10th day after dosing. Synthetic pyrethroids caused slight tremours in the whole body accompanied by salivation. In general, hyperactivity to external stimuli and loss of appetite and body weight were also observed.

With sab‐acute oral doses, Permasect‐25 EC (Form.) more potently affected haemoglobin (Hb), red cell (RBC) counts and chloride level. Cypermethrin‐92 (Tech.) was most potent towards thrombocytes and clotting time. Azodrin‐71 (Tech.) was more potent to white cell (WBC) counts and serum protein level.

The present Haematological studies have disclosed the possible reaction of blood and blood ferming organs to these insecticides.
Inhibition of hepatic microsomal lipid peroxidation by endogenous glycogen in the rat
Authors: Iba Michael M.
Published: October 2006

The effect of endogenous glycogen on lipid peroxidation was examined in hepatic microsomes from rats. Microsomes were prepared to retain endogenous hepatic glycogen (P) or to minimize it (P). The indices of lipid peroxidation examined included the rate of NADPH‐dependent formation of malondialdehyde (MDA) and the concomitant destruction of cytochrome P‐450 and decline in the linearity of benzphetamine N‐demethylase activity in microsomes. Cytochrome P‐450 was destroyed during benzphetamine N‐demethylation in microsomes with the loss being more extensive in P than in P. The destruction of cytochrome P‐450 and the concomitant loss in linearity of benzphetamine N‐demethylation in P were prevented by added EDTA. Added linoleic acid hydroperoxide (LAHP) also caused a time‐dependent loss of cytochrome P‐450 in microsomes with the rate being greater in P than in P. The results show that glycogen inhibits hepatic microsomal lipid peroxidation and suggest that variations in glycogen content may contribute to disparities in in vitro oxidative activities between different microsomal samples. Such disparities may be minimized by the removal of glycogen during the preparation of microsomes and then supplementing the incubation mixtures with EDTA. The in vivo relevance of the observed antioxidant effect of glycogen is discussed in terms of the possible modulation by the polysaccharide of hepatotoxicity by agents whose effects may be mediated by lipid peroxidation.
Preliminary evaluation of treatment and selection conditions which affect expression of anthracycline mutagenicity in Salmonella typhimurium and a diploid human lymphoblast cell line
Authors: Thomas Harvey F.
Published: October 2006

Mutagenic potency in the Ames Salmonella test is an important endpoint that can be influenced by biological and technical factors. The ranking of mutagenic activity of a series of anthracyclines was measured using different conditions of exposure and mutation selection. A 20 min preincubation treatment version of the Ames test using a 0.2–2.0 μg/ml (0.36–3.60 nM/ml) dose range of each of the anthracyclines Adriamycin, Daunomycin, Carminomycin, 4′‐O‐methyldoxorubicin and 4‐demethoxydoxorubicin confirmed the order of mutagenic potency seen with the same compounds under direct plating conditions. Preincubation results also confirm direct‐plating results by showing the greater sensitivity of selection to His+ reversion over 8‐azaguanine resistance to anthracycline mutagenicity. However, the order of mutagenic potency was changed by lengthening the preincubation treatment time to 2 h or reducing the population density of the treated cell inoculum by ten fold. These results suggest that certain treatment conditions enable the treated cells to diminish the phenotypic expression of anthracycline mutagenicity. For comparative purposes, daunomycin and Adriamycin mutagenicity in response to 0.1–0.2 nM/ml and 0.1–0.3 nM/ml dose ranges, respectively, were assessed in a human cell culture system with 6‐thioguanine and 5‐trifluorothymidine forward mutation selection. A daunomycin dose of 0.1 nM/ml generated approximately 25‐fold and 20‐fold increases in mutant fraction with 6‐thioguanine and 5‐trifluorothymidine selections, respectively. Equivalent dosing with Adriamycin generated approximately a 4‐fold increase in mutant fraction with 6‐thioguanine selection and little or no increase with 5‐trifluothymidine selection. Maximum increase in expression of mutant fraction within the anthracycline treated populations of cells occurred with a 10 day expression time. Plating for clone forming ability on the day of treatment showed that a standard 0.1 nM/ml treatment dose reduced cloning efficiency of the daunomycin treated cells by 90% and reduced the clone forming ability of the Adriamycin treated cells by 30%.
The post‐natal fate of supernumerary ribs in rat teratogenicity studies
Authors: Wickramaratne G. A.
Published: October 2006

A common occurrence in rat teratology studies, supernumerary ribs, have been considered to be indicative of teratogenicity by some authors but not to be so indicative by others. As a teratogenic event is, by definition a permanent change, a study to follow the fate of supernumerary ribs in the development to adulthood of the rat was undertaken. An established teratogen in the rat, aspirin, was used to increase the frequency of supernumerary ribs. Even though aspirin treatment of the dams doubled the initial frequency of supernumerary ribs the results show that over the first 60 days post‐partum their frequency in both control and treated groups decline to essentially zero. This decline in frequency of supernumerary ribs is complemented by an increase in the proportion of foetuses with a fully developed transverse process on the first lumbar vertebra. The proposal that supernumerary ribs in the rat are a result of developmental delays in a labile region of the axial skeleton and not a manifestation of a teratogenic event is presented.
Evaluation of the division arrest method of the CHO/HGPRT mutation assay
Authors: Oshiro Y. , Balwierz P. S. , Piper C. E.
Published: October 2006

We have evaluated the division arrest method of the CHO/HGPRT mutation assay following the procedure described by O'Neill et al. Environ. Mutagen. 4, 421–434 (1982). This method simplifies the culture manipulations required during the expression period and can be readily adopted for screening mutagenic compounds. The mutation frequencies derived from the subculture method and the division arrest (no subculture) method after treatment of CHO‐K1BH4 cells with ethyl methanesulfonate were similar at all concentrations. The background mutation frequencies observed in the medium and solvent (0.5% DMSO) controls ranged from 0 to 9 colonies per 1 × 106 cells. Twenty to 24 h treatments, using the direct‐acting compounds ethyl methanesulfonate, N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, ICR‐191 acridine, 5‐Bromo‐2′‐deoxyuridine, mitomycin C and high concentrations of thymidine produced positive mutagenic responses, while 2′‐deoxyuridine and trifluorothymidine gave negative responses. Four‐h treatments with Benzo[a]pyrene, diethylnitrosamine, 2−acetylaminofluorene, 3‐methylcholanthrene and 2‐aminoanthracene in the presence of S9 also produced positive results. Anthracene, fluorene and pyrene with S9 were negative. However we found that a toxic, non‐mutagenic compound (anthracene) can yield sporadic increases in mutation frequencies (1 out of 10 replicates). Overall, our results indicate that the division arrest method of the CHO/HGPRT mutation assay can be reliably used for routine screening.