bluuebunny/crossref_metadata_2025_split huggingface dataset:
The assessment of chemically induced liver injury in rats
Authors: Pritchard D. J. , Wright M. G. , Sulsh S. , Butler W. H. 
Published: October 2006

AbstractThe object of this investigation was to study the relationship between acute hepatic injury and blood coagulation. Most of the clotting factors are synthesised by the hepatocytes and therefore it would seem likely that hepatic injury would lead to an impairment of blood clotting.Dimethylnitrosamine (DMN) and carbon tetrachloride (CCI4) were selected as model hepatotoxins to induce an acute hepatic lesion. Single doses of each compound were administered to male rats and groups of animals killed 3, 6, 16 and 24 h later in order to study the morphological development of the lesion and to relate this to changes in the haematological profiles. Both compounds produced a centrilobular necrosis, but with DMN there was a haemorrhagic component due to damage to endothelial cells, which contrasts with the classical coagulative necrosis produced by CCI4. After 6 h apoptosis was commonly seen in the centrilobular areas of the DMN treated rats. This process of cell death has not previously been demonstrated in chemically induced acute hepatic injury and was not seen in the CCI4 treated rats. Significantly prolonged clotting times were seen in both DMN and CCI4 treated rats and occurred in parallel with some of the early morphological changes but prior to the appearance of extensive haemorrhagic or coagulative necrosis. This preliminary data suggests that the measurement of blood coagulation times may provide a relatively specific and sensitive indicator of acute hepatic injury in rats.
Development of a reconstituted water medium and preliminary validation of the Frog Embryo Teratogenesis Assay—Xenopus (FETAX)
Authors: Dawson Douglas A. , Bantle John A. 
Published: October 2006

AbstractA reconstituted water medium was developed for use in the Frog Embryo Teratogenesis Assay—Xenopus (FETAX). FETAX solution was then tested on three compounds with known mammalian teratogenicity (ethanol, caffeine, and 5‐fluorouracil) as was a non‐teratogen (saccharin). The results obtained were then compared with results from tests on these compounds in two other media that had previously been used in the assay. Saccharin was not teratogenic. Ethanol and caffeine were weak and moderate teratogens, respectively. 5‐fluorouracil was a strong teratogen. The results compare favorably with those obtained in mammalian studies. The amount of growth inhibition in embryos in the 96 h tests was positively correlated with the degree of teratogenicity of the compound. Final validation of FETAX will allow it to be used to screen and rank compounds for further testing and as a tool for studying the basic mechanisms of teratogenesis.
Studies on γ‐glutamyl transpeptidase (GGT) after Di(2‐ethylhexyl) phthalate (DEHP) exposure
Authors: Parmar Devendra , Srivastava Satya P. , Seth Prahlad K. 
Published: October 2006

AbstractAdministration of Di(2‐ethylhexyl)phthalate (DEHP) at doses of 250, 500, 1000 and 2000 mg/kg to adult rats was found to significantly increase the activity of γ‐glutamyl transpeptidase (GGT) in liver and serum in a dose‐dependent manner. The data indicate that DEHP can be hepatotoxic since an increase in serum GGT levels are indicative of hepatobiliary dysfunction and liver malignancy. An assay of GGT in serum of the individuals exposed to DEHP could be helpful in early detection of liver disorders due to this widely used plasticizer.
Time‐course studies of the distribution of [1–14C] acrylonitrile in rats after intravenous administration
Authors: Silver E. H. , Szabo S. , Cahill M. , Jaeger R. J. 
Published: October 2006

AbstractIntravenous injection of acrylonitrile (ACN) causes adrenal hemorrhagic necrosis. ACN and its metabolites react with glutathione and bind covalently with macromolecules. Hence the purpose of this investigation was to measure the distribution and covalent binding of radiolabel derived from [1‐14C]ACN in order to detemine whether binding of ACN or its metabolites may be implicated in the pathogenesis of ACN‐induced adrenal injury. Following intravenous injections of ACN, concentrations of total radiolabel were highest in the blood, liver, duodenum, kidneys, and adrenals. Except for blood, there was a time‐dependent decrease in total radiolabel in these tissues. Compared with other major organ systems, the levels of covalently bound radiolabel were lower in the adrenal glands. These results do not support a role of covalent binding of ACN or its metabolites in the adrenal toxicity of ACN, but suggest that the initial high concentrations of total radiolabelled compounds derived from ACN could play a role in the action of ACN on the adrenal glands.
Acute inhalation toxicity of 3,3‐dimethyl‐2‐butanol in sprague‐dawley rats
Authors: James John T. , Infiesto Bernardita P. , Landauer Michael R. 
Published: October 2006

AbstractSprague‐Dawley rats were given 15, 70 and 140 min exposures to 15 mg/l 3,3‐dimethyl‐2‐butanol, pinacolyl alcohol (PA), or 6‐hour exposures to 0.2, 1.0 and 5.0 mg/l PA (1 mg/l = 240 ppm). A 50% mortality rate was obtained at the longest exposure to 15 mg/l. Sex related differences in the blood levels of PA and pinacolone were noted, and the surviving male rats failed to gain weight normally in the first week after exposure. In rats exposed to 5.0 mg/l for 6 hours, there were reductions in horizontal and vertical activity and the minute volume was 55% of controls at the end of exposure. Like many secondary alcohols, PA poses only a possible Inhalation hazard; however, male rats may be somewhat more susceptible than females.
Subchronic dermal toxicity studies of alcide Allay® gel and liquid in rabbits
Authors: Abdel‐Rahman Mohamed S. , Skowronski Gloria A. , Turkall Rita M. , Gerges Samy E. , Kadry Abdel‐Razak , Abu‐Hadeed Ali H. 
Published: October 2006

AbstractAlcide® is a germicidal agent which is highly effective in killing a wide range of bacteria and fungi. 2.0 g kg−1 Allay® gel or placebo were applied once per day while 3.0 g kg−1 Allay® liquid or placebo were administered three times per day over a 30 day period to the skin of albino rabbits. Allay® gel and liquid contained either of two concentrations of sodium chlorite and lactic acid as active ingredients. The concentration of active ingredients, sodium chlorite and lactic acid, in the low dose gel was 25% of high dose gel and low dose liquid was 60% of high dose liquid. Moderate to severe erythema was observed only in the high dose gel group after 7 days of treatment, but skin appeared visibly normal by day 18. Histologically fixed skin at day 30, however, showed inflammatory changes in the high and low dose gel groups and hyperkeratosis in all gel groups. At the termination of the study, mean corpuscular hemoglobin concentration decreased significantly in the Allay® gel and liquid groups compared to an untreated control group. In all gel treatments, BUN/creatinine levels decreased significantly. Hematology and clinical chemistry parameters, however, were within the normal range of values for the gel and liquid groups, indicating no clinically significant changes due to Allay® treatment. Pancreas/body weight ratios were significantly reduced in all gel groups, while spleen, pancreas and ovary/body weight ratios were significantly higher in both liquid dosage groups. No histotogical changes were observed in any of these organs.
One‐year inhalation toxicity study of formaldehyde in male rats with a damaged or undamaged nasal mucosa
Authors: Appelman L. M. , Woutersen R. A. , Zwart A. , Falke H. E. , Feron V. J. 
Published: October 2006

AbstractTo study the effect of bilateral intranasal electrocoagulation damage on the susceptibility of rats to formaldehyde vapour, male Wistar rats with a damaged or undamaged nasal mucosa were exposed to atmospheres containing 0, 0.1, 1 or 10 ppm formaldehyde vapour during 6 h/day, 5 days/wk for 13 or 52 weeks.Electrocoagulation damage was induced in the anterior third part of the nose. The repair process followed the pattern of wound healing. Loss of turbinates and perforation of the septum were common irreversible findings. After 13 weeks basal cell hyperplasia and squamous metaplasia of the respiratory epithelium, and rhinitis were still visible. After 52 weeks effects attributable to electrocoagulation were slight basal cell hyperplasia and some rhinitis. Major formaldehyde‐related adverse effects in the 10 ppm group not subjected to electrocoagulation included growth retardation, reduced urine production, and rhinitis accompanied by squamous metaplasia of the nasal respiratory epithelium. No adverse effects were seen at 0.1 or 1 ppm in rats with an intact nasal mucosa.The principal untoward effects of formaldehyde in electrocoagulation‐treated rats seen after 13 and/or 52 weeks comprised increase in basal cell hyperplasia, squamous metaplasia of the nasal respiratory epithelium, damage to the olfactory epithelium at 10 ppm, and focal squamous metaplasia of nasal respiratory epithelium at 0.1 and 1 ppm.Major conclusions were: (a) the rat nose damaged by electrocoagulation is more susceptible to the cytotoxic action of formaldehyde than the undamaged nose, (b) 10 ppm formaldehyde has no adverse effect on organs remote to the site of entry in rats with an undamaged nose, and (c) 1 ppm formaldehyde did not visibly affect the intact nasal epithelium.
Nucleophilic index value: Implication in the protection by indole‐3‐carbinol from N‐nitrosodimethylamine cyto and genotoxicity in mouse liver
Authors: Shertzer H. G. , Tabor M. W. 
Published: October 2006

AbstractA novel assay system was developed in order to quantitate the nucleophilicity of pure chemicals or tissue extracts. This Nucleophilic Index Value (NIV) assay was based on the ability of putative nucleophiles to inhibit the methylation of cysteine by limiting concentrations of the electrophilic source, N‐methyl‐N‐nitrosourea (MNU). Efficacy of model and cellular nucleophiles was quantitated as nmol cysteine protected by the nucleophile from methylation by MNU/h/mM compound. The NIVs of the pure compounds ascorbate, glutathione, 4‐(4‐nitrobenzyl)‐pyridine (NBP) and indole‐3‐carbinol (I‐3‐C) were 2400, 1600, 3 and 0, respectively. When mice were treated with I‐3‐C by gavage at dosages of 0, 25, 50, 75 or 100 mg/kg body wt, the NIV for ethyl acetate extracts of the livers 1 h after treatment were 0, 33, 47, 52 and 92 nmol cysteine preserved/h/g tissue, respectively. The I‐3‐C enhancement of NIV was not attributable to ascorbate or glutathione, neither of which were present in the ethyl acetate extracts of liver. When mice were treated with 10 mg N‐nitrosodimethylamine (NDMA)/kg body wt 1 h after the varying dosages of I‐3‐C, the 24 h post‐NDMA plasma alanine transaminase (ALT) values were decreased by I‐3‐C pretreatment in a dose‐dependent fashion. Plasma ALT values were used in this study as an indicator of hepatotoxicity. The coefficient of determination, r2, computed from the linear least squares correlation coefficient between NIV and ALT values, was 0.80 (0–100 mg I‐3‐C/kg) and 0.97 (0–75 mg/kg). In addition to cytological protection from NDMA toxicity, I‐3‐C pretreatment significantly reduced NDMA mediated DNA single strand breakage. The degree of protection was about 60% for both NDMA mediated ALT release and DNA strand breakage. The data are consistent with the hypothesis that I‐3‐C in vivo provides protection from NDMA cyto and genotoxicity by virtue of enhancing the ability of the hepatocyte to scavenge reactive electrophiles, thus protecting cellular nucleophilic sites that are critical for normal function.
The evaluation of HBDH and LDH isoenzymes in cardiac cell necrosis of the rat
Authors: Barrett R. J. , Harleman J. H. , Joseph E. C. 
Published: October 2006

AbstractThe total LDH, HBDH and LDH isoenzyme activities were assessed in a number of rat tissues. HBDH did not correlate with LD1 and LD2 isoenzyme activity in tissues with high HBDH activity. HBDH therefore cannot be used as a marker for cardiac necrosis in the rat. In rats treated with isoprenaline and SK&F 94120 at doses producing myocardial necrosis, only the LD1 isoenzymes showed any significant change but only within the first 24 h of treatment. No statistically significant differences were seen in the plasma AST, CK, CK‐MB and total LDH activities.
Experimental design for the C3H/10T½ CL8 cell transformation assay
Authors: Oshiro Y. , Balwierz P. S. , Piper C. E. 
Published: October 2006

AbstractThe C3H/10T1/2 CL8(10T½) cell transformation assay has been used as an important in vitro tool for screening potential carcinogens. In this paper we describe an experimental design that increases the sensitivity and specificity of the assay. One half of the total dishes was allocated to the solvent control and the other half was equally subdivided into four treatment dose groups of low to high cytotoxic effects. The transformation frequency was calculated on the basis of the number of dishes with Type III foci. Each treatment group, as well as the pooled treatment groups, was compared to the solvent control using Fisher's exact test. The sensitivity of our design, as evaluated by power analyses, greatly exceeded that of a standard test design in which about 20 dishes are allocated to each of the control and treatment groups. Furthermore, our use of an expanded number of control and treatment dishes reduces the chance for both false positive and false negative responses. Our experimental design is illustrated with data from experiments in which the transforming potential of two drugs, dimenhydrinate and SC‐32006, was examined.
The effects of carbon monoxide on persistent changes in young rat heart: Cardiomegaly, tachycardia and altered DNA content
Authors: Penney David G. , Gargulinski Richard B. , Hawkins Beverly J. , Santini Ronald , Caldwell‐Ayre Theresa M. , Davidson Scott B. 
Published: October 2006

AbstractNewborn rat pups that inhale 500 ppm carbon monoxide (CO) for 32 days and develop increased heart mass (i.e. cardiomegaly) show persistent cardiomegaly and elevated resting heart rate as adults. Studies were carried out to explore the relationship of these phenomena to CO concentration and initial cardiomegaly using exposures of 350, 500 and 700 ppm CO. Initial cardiomegaly was greater in the right ventricle free wall (RV) than in the left ventricle plus interventricular septum (LV+S) at all three CO concentrations, and RV mass excess increased with CO concentration. Initial RV cardiomegaly was greater at 350 and 700 ppm CO in females than in males. Persistent cardiomegaly in the RV also increased with CO concentration, and was significantly greater in the females. Persistent cardiomegaly in the RV increased with initial cardiomegaly but at a decreasing rate at the higher CO concentrations, and when expressed as a percentage of initial cardiomegaly (i.e. “efficiency”), the relative response was greatest at 500 ppm CO. For LV+S, efficiency of development of persistent cardiomegaly was greatest at 350 ppm CO. Persistent tachycardia increased with CO concentration in males but failed to do so in females, and was only weakly correlated with degree of persistent cardiomegaly. Thus, persistent cardiomegaly and persistent tachycardia (in males) are related to CO concentration. Myocardial DNA content of 32‐day‐old juveniles was significantly increased at 350 and 700 ppm CO. Adult DNA content of the RV was significantly elevated at 350 ppm CO (females) and continued to rise with CO concentration. DNA concentrations of the RV and LV were increased at 700 ppm CO. The case is argued that altered cardiac DNA content and concentration indicates persistent cellular‐level changes (i.e. ‘cellular remodeling’), also related to CO concentration.
Protection against carbon tetrachloride‐induced hepatotoxicity by protein A
Authors: Singh K. P. , Saxena A. K. , Zaidi S. I. A. , Dwivedi P. D. , Srivastava S. P. , Seth P. K. , Ray P. K. 
Published: October 2006

AbstractProtection from carbon tetrachloride (CCl4)‐induced hepatotoxicity by protein A was assessed histologically in rats. Carbon tetrachloride exposure produced swollen, vacuolated and necrotic cells in the centrilobular region of the hepatocyte in rats. Animals given protein A prior to and during CCl4 treatment showed a complete absence of hepatic lesions. Our study showed that protein A, a potent immunomodulator, has the potential to reduce liver injury caused by carbon tetrachloride, a known hepatotoxin in the rat.
Assessment of the relative hazard involved with airborne irritants with additional hepatotoxic or nephrotoxic properties in mice
Authors: de Ceaurriz J. , Gagnaire F. , Ban M. , Bonnet P. 
Published: October 2006

AbstractThis paper deals with the conversion of the hepatotoxicity of 1,2‐dichlorobenzene (DCB), the nephrotoxicity of hexachloro‐1,3‐butadiene (HCBD) and the respiratory effects of these two toxicants into quantal data. It aims to provide some useful information on the best strategy used for safety evaluation. A reflex bradypnea indicative of irritation of the nasal cavities of mice occurred during a 15‐min oronasal exposure to each chemical. A reduction in the development of staining for liver glucose‐6‐phosphatase (G6‐phosphatase) and an increase in the number of damaged tubules in cryostat kidney sections stained for alkaline phosphatase were the measure of toxicity in mice subjected to a whole‐body 4‐h exposure to DCB and HCBD vapours, respectively. The immediate irritant responses, as well as the delayed liver and kidney responses, were measured at the peak of the chemical's action. These maximum responses were then used to establish the relationships of exposure level effects and also the median active levels of exposure (MALs). The DCB and HCBD MALs responsible for a 50% decrease in the respiratory rate of mice (RD50) were 181 and 211 ppm, respectively. The MAL required for eliciting a 50% decrease in G6‐phosphatase staining intensity in DCB‐exposed mice was 598 ppm and that associated with 50% of damaged tubules in HCBD‐exposed mice was 7.2 ppm. On the basis of these quantitative data, potency ratios indicated that irritation and kidney injury are the primary manifestations of toxicity associated with short‐term exposure to DCB and HCBD, respectively. It is suggested that profiles of acute toxicity similar to that of DCB or HCBD may be useful in assessing the relative hazard involved with airborne chemicals.
Control of nephrotoxicity in the rat during repeated cis‐platinum treatments
Authors: Jones Mark M. , Basinger Mark A. 
Published: October 2006

AbstractThe nephrotoxicity of cis‐platinum (CDDP) in the rat can be controlled throughout a series of weekly administrations of CDDP (each of 5 mg kg−1, i.v.) for at least three weeks by a combination of protective measures involving pretreatment with dithiocarbamates and diuretics and the administration of appropriate dithiocarbamates given 1h after the CDDP. The use of dithiocarbamates with polar substitutents is effective in removing both renal and hepatic deposits of platinum from rats subsequent to its administration and in this respect these compounds are significantly superior to meso‐2,3‐dimercaptosuccinic acid (DMSA) in the rate at which platinum is removed and in the amounts removed. The most effective of the dithiocarbamates remove ca. 70% of the platinum from the kidneys and the liver; the least effective remove ca. 50% of the platinum from these organs when given at a level of 1.57 mmol kg−1 i.p. for 6 days subsequent to the administration of CDDP. Acetazolamide was shown to be much less effective in preventing renal damage than the dithiocarbamates and was not effective in reducing renal or hepatic levels of platinum. Pretreatment with sodium diethyldithiocarbamate 12h prior to the administration of the CDDP was more effective in preventing renal damage than the administration of this compound 30 min before the cis‐platinum. Several dithiocarbamates are found to be superior to sodium diethyldithiocarbamate in reducing renal platinum burdens of rats given CDDP at the level of 6 mg kg−1, and dose—response curves for the removal of renal and hepatic platinum were determined for sodium N‐methyl‐D‐glucamine dithiocarbamate (NaG). The use of dithiocarbamates, other than sodium diethyldithiocarbamate, to control the nephrotoxicity of CDDP may possess some advantages in the clinic.
Mechanism of testicular atrophy induced by Di‐n‐butyl phthalate in rats. Part 1
Authors: Fukuoka Masamichi , Tanimoto Tsuyoshi , Zhou Yu , Kawasaki Nana , Tanaka Akira , Ikemoto Isao , Machida Toyohei 
Published: October 2006

AbstractRepeated oral doses of di‐n‐butyl phthalate (DBP) to male rats caused a decrease in testicular fructose and glucose and a sloughing of the germ cells on the first day of treatment. On day 2, more severe sloughing was seen and was accompanied by decreases in testicular iron and zinc levels and increases in the level of inositol and cholesterols. The sloughing was followed by atrophy, accompanied by dissociation of the germ cells from the Sertoli cells and reduction of triglycerides, cholesterols and phospholipids containing choline and ethanolamine residues in the testis.
A versatile mercury vapour generating system suitable for long‐term inhalation experiments
Authors: Magos L. , Hudson A. R. 
Published: October 2006

AbstractA mercury vapour generating system is described that is based on the reduction of HgCI2 by SnCI2 in the input airstream of the inhalation chamber. The solutions of the two chemicals are pumped by peristaltic pumps from reservoirs through a miniature mixing chamber into the upper part of a sloping glass tube (reduction chamber) through which air is sucked into the inhalation assembly. The liquid flows down the slope and through a port into a Quickfit flask. Reservoirs can be filled and the collecting flask emptied without interruption of exposure. The desired vapour concentration is achieved by varying the rate of mercury injection and the rate of airflow. Concentration in the inhalation chamber can be measured by passing air through a mercury vapour monitor or by radioactivity when 203HgCI2 is used and a known volume of air is passed through a hopcalite absorber. Operation instructions and an experimental example with mice are given.
Nasal irritation and pulmonary toxicity of aliphatic amines in mice
Authors: Gagnaire F. , Azim S. , Bonnet P. , Simon P. , Guenier J. P. , De Ceaurriz J. 
Published: October 2006

AbstractThe expiratory bradypnoea indicative of upper airway irritation in mice was evaluated during a 15‐min oronasal exposure to increasing concentrations of twenty aliphatic amines. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each test compound. Moreover, eight out of the twenty amines were tested for pulmonary toxicity in mice and for the effects of a 120‐min exposure on the respiratory rates of non‐anaesthetized, traheally cannulated mice (RD50TC). Both allylamine and diallylamine showed RD50 values of 9 ppm and 4 ppm, respectively, while the RD50 values associated with exposure to saturated amines ranged from 50 to 200 ppm. Among the eight amines tested for both upper airway irritation and pulmonary toxicity, diisopropylamine and di‐n‐butylamine showed a RD50TC/RD50 ratio of <1, indicating that the respiratory toxicity induced by these two amines would be related primarily to pulmonary effects. On the basis of prior predictions proposed for upper airway irritants, tentative standards are given for ten amines. Moreover, it is suggested that the basis of standards for industrial exposure to diisopropylamine and di‐n‐butylamine should be specified.