bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two‐year toxicity and carcinogenicity study of acrolein in rats
Authors: Parent Richard A. , Caravello Halina E. , Long James E. 
Published: October 2006

AbstractFive‐hundred and sixty Sprague‐Dawley rats were randomized into one control and three treatment groups (70 of each sex per group). Animals were treated by daiiy gavage with 0.0, 0.05, 0.5 and 2.5 mg kg−1 acrokin in water (10 ml kg−1). These dosing levels were selected as a result ofa 6‐week range‐finding study. Ten rats of each sex per group were sacrificed at 1 year, and the remainder of the animals were treated for 102 weeks. Daily observations were made, and various clinical, hematological and urine parameters were measured after 3, 6, 12 and 18 months of treatment and immediately prior to termination. All animals, whether found dead or sacrificed, were subject to necropsy and both absolute and relative organ weights were recorded. An extensive array of tissues were examined microscopically for all test animals.The only effects noted for treated rats that were statistically different from controls were consistent depression of creatinine phosphokinase levels, which was difficult to explain, and consistent increases in early cumulative mortalities in both males and females. There was no significantly increased incidence of microscopic lesions in treated rats, whether neoplastic or non‐neoplastic. This study clearly demonstrates the lack of neoplastic response in Sprague‐Dawley rats as a result of being treated with acrolein by gavage.
Failure of N‐Acetylcysteine to reduce alpha amanitin toxicity
Authors: Schneider Sandra M. , Michelson Edward A. , Vanscoy Gordon 
Published: October 2006

AbstractAcetaminophen undergoes toxic conversion in the liver to a free‐radical intermediary which binds to glutathione. N‐Acetylcysteine acts as a glutathione precursor when natural stores are depleted, and is an effective antidote for acetaminophen overdose. Mushrooms containing amatoxins (such as Amanita phalloides) may undergo similar toxic conversion. However, in our amatoxin‐poisoned mouse model, N‐acetylcysteine (1.2 g kg−1) produced no change in survival or hepatic enzyme elevation compared to control animals. We conclude that N‐acetylcysteine has no clinical role in the treatment of Amanita phalloides ingestion.
Promotional activities of the non‐genotoxic carcinogen bemitradine (SC‐33643)
Authors: Gad Shayne C. , Burton Earl , Chengelis Christopher P. , Levin Stuart , Piper Charles E. , Oshiro Yuki , Semler David E. 
Published: October 2006

AbstractBemitradine (SC‐33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2‐year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg−1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body weights were decreased compared to controls: 5–15% in the female and 10–12% in the male dosage groups by week 105 of the study. Prolactin values were significantly increased in 150 and 450 mg kg−1 females. The compound caused significant increased incidences of liver, thyroid (both sexes) and mammary (females only) neoplasms.The metabolism of bemitradine was studied in both rats and man. Bemitradine and its primary metabolite (SC‐36741; desethylbemitradine) were tested and found to be non‐genotoxic in Ames, rat primary hepatocyte UDS, CHO/HGPRT, CHO cytogenetics, in vivo mouse micronucleus and mouse lymphoma TK+/− (bemitradine only) assays.Finally, in an altered hepatic foci (Y‐glutamyl transpeptidase positive) promotion assay in female Charles River CD rats, bemitradine was found to be a promotor, though not as potent as phenobarbital.We concluded that bemitradine (which has been dropped from development) is a non‐genotoxic carcinogen which appears to act by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands. Tumors seen in the thyroid were probably secondary to the effects of bemitradine on metabolism.
Effects of palytoxin on porcine coronary artery rings
Authors: Robinson Casey P. , Franz David R. , Bondura Maria E. 
Published: October 2006

AbstractPalytoxin, in concentrations as low as 100 fM, caused contractions of porcine coronary artery rings. Palytoxin concentrations of < 1 nM caused slowly developing contractions which were not maximal even after 2 h. Rings contracted by 100 nM palytoxin achieved maximal tension by 10 min and relaxed to 53% of that maximum after 2 h. Verapamil (1 μM) reduced the rate of contractions induced by 10 nM palytoxin. Exposure of rings to > 10 nM palytoxin for 1–2 h reduced contractions to potassium 18 h later to 61% of the expected contraction and abolished those to palytoxin administered later. Both 10 and 100 nM palytoxin depleted potassium from coronary artery rings. Verapamil (10 μM) prevented potassium depletion by 10 nM palytoxin, but neither 10 μM verapamil nor 1 μM nifedipine prevented potassium depletion in rings exposed to 100 nM palytoxin. Thus, the contractile action and the potassium depleting action of palytoxin on the porcine coronary artery involve mobilization of nifedipine‐ and verapamil‐sensitive calcium. Verapamil‐ and nifedipine‐sensitive calcium was not required for depletion of potassium by the highest PTX concentration (100 nM), however.
Cytogenetic analysis of pulmonary lavage and bone marrow cells of rats after repeated formaldehyde inhalation
Authors: Dallas Cham E. , Scott Michael J. , Ward Jonathan B. , Theiss Jeffrey C. 
Published: October 2006

AbstractCytogenetic analyses were conducted on bone marrow and pulmonary lavage cells from rats that received repeated inhalation exposures to formaldehyde. Male Sprague‐Dawley rats were exposed to 0, 0.5, 3, or 15 ppm formaldehyde for 6 h per day, 5 days per week, for 1 and 8 weeks. There was no significant increase in chromosomal abnormalities in the bone marrow cells of formaldehyde‐exposed rats relative to controls. There was a statistically significant increase in chromosomal aberrations in the pulmonary lavage cells from rats that inhaled 15 ppm. There were 7.6 and 9.2% of the scored pulmonary lavage cells that had aberrations following 1 and 8 weeks, respectively, of 15 ppm formaldehyde exposure (with control levels of 3.5 and 4.8%, respectively). The predominant damage seen was chromatid breaks. These findings indicate that marginal but statistically significant genotoxic effects could be detected locally in lung alveolar macrophages, but not distally in bone marrow, following repeated formaldehyde exposures only at a high concentration that is carcinogenic to rats. The biological significance of this effect is uncertain since formaldehyde is not considered to be a lung carcinogen in rats.
Renal effects of N‐(3,5‐disubstitutedphenyl)‐succinimides in the fischer 344 rat
Authors: Rankin Gary O. , Teets Vonda J. , Shih Hsiencheng , Beers Kelly W. , Nicoll Derek W. , Anestis Dianne K. , Brown Patrick I. , Hubbard John L. 
Published: October 2006

AbstractPrevious studies have demonstrated the importance of substitution at the 3‐ and 5‐positions of the phenyl ring in N‐phenylsuccinimides for the production of nephrotoxicarrts in this series of compounds. The purpose of this study was to determine if the electronic nature of the 3,5‐substituents is an important determinant for nephrotoxic potential. Male Fischer 344 rats (four rats per group) were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol kg−1) or vehicle, and the renal function was monitored for 48 h. Only N‐(3,5‐dichlorophenyl)succinimide (0.4 or 1.0 mmol kg−1) induced marked changes in renal function. Urine volume, BUN concentration and proteinuria were increased following N‐(3,5‐dinitrophenyl)succinimide (1.0 mmol kg−1) treatment but other renal parameters and renal morphology were unchanged in this treatment group. These results indicate that the presence of halogen atoms atthe 3‐ and 5‐positioiis of the phenyl nag in N‐phenylsuccinimides is more important for nephrotoxic potential than the presence of non‐halogen substituents. The reason why halogen substitution is an important determinant for N‐phenylsuccinimide nephrotoxicity is unknown.
Distribution to the fetus and major organs of the rat following inhalation exposure to pyrene
Authors: Withey J. R. , Shedden J. , Law F. P. C. , Abedini S. 
Published: October 2006

AbstractConcentrations of pyrene and total metabolites were determined for individual fetuses and selected maternal organs and tissues immediately and 6 h followinga 95‐min head‐only exposure of pregnant Wistar rats, on gestation day 17, to five levels of pyrene over therange 200–800 mg m3 as a microcondensation aerosol. The influence of uterine horn, side and position, on distribution to the fetus was assessed. The concentration of both pyrene and its metabolites increased more over the exposure range (eightfold) than did those in the fetus. Concentrations of pyrene or its metabolites in fetal tissues were not found to be related to its position on the uterine horn. There was an unexplained and significant (P < 0.01) higher concentration of pyrene in fetuses on the right side relative to the left side of the uterine horn for the animals killed immediately following exposure.A comparison of the levels in maternal tissues measured immediately following the exposure and 6 h later showed that there was some redistribution of pyrene and its metabolites to the fat tissues, i.e. levels in the fat increased over the 6 h period following the exposure. Levels in the other tissues diminished dmmg this period. In general, concentrations of pyrene and its metabolites were lowest in the fetal tissues relative to those in the sampled maternal organs and tissues.
In vivo evaluation of airway and pulmonary tissue response to inhaled methacholine in the rat
Authors: Sakae R. S. , Martins M. A. , Criado P. M. P. , Zin W. A. , Saldiva P. H. N. 
Published: October 2006

AbstractThe current study was designed to assess the methacholine dose‐response behaviour of the airways and pulmonary parenchyma with the aid of alveolar capsules. The experiments were performed in eight adult female Wistar rats (155–250 g). The animals were anaesthetized with sodium pentobarbital (30 mg kg−1 i.p.) and mechanically ventilated. Measurements of tracheal (ptr) and alveolar (pA) pressures and the pressure change across the airway (paw) were performed prior to and after exposing rats to aerosols generated from sequentially increasing concentrations of methacholine chloride solution (2, 4, 8, 16, 32, 64 and 128 mg ml−1) through the breathing circuit. Baseline paw and pA mean (± SD) values (6.44 ± 2.06 and 8.25 ± 3.44 cmH2O, respectively) were not statistically different (P = 0.220). The increases in ptr and pA were significant during the dose‐response study (P = 0.001), whereas paw was not increased. The increase in pA was significantly higher than that of paw (P < 0.001). The relationship between the mean (± SE) values of ptr and pA could be well described by a straight line (r = 0.990, P < 0.001). There were also significant correlations based on regression equations between ptr and paw (r = 0.947, P < 0.001) and pA and paw (r = 0.913, P = 0.004). These findings suggest that the pulmonary tissue of rats is a major component responsible for the increase in lung impedance observed after methacholine challenge. In addition, airway and pulmonary parenchyma pressure changes were correlated, suggesting that both lung regions have a similar sensitivity to the agonist. Our results indicate that the response of peripheral tissues should be considered during bronchial challenge protocols in rats.
Toxicology of carbaryl and aldicarb on brain and limb cultures of chick embryos
Authors: Farage‐Elawar M. , Rowles T. K. 
Published: October 2006

AbstractA variety of carbamates have been developed since the 1960s for use as broad‐spectrum insecticides. An easy and inexpensive in vitro assay using chick‐embryo derived cells was examined for its capability to screen and test the toxicity of these compounds. Chick embryo brain and limb bud cultures were treated with different concentrations of either carbaryl or aldicarb with or without activation (± S‐9) for 5 days. Viability and cytotoxicity using the neutral red assay, and carbamate effects on cell migration and colony spread were measured. S‐9 decreased the effects of carbaryl and aldicarb on brain cell cytotoxicity at exposures of 15–60 ppm and 40–200 ppm, respectively, as indicated by increased concentrations of neutral red. Viability of brain cell cultures was not altered by aldicarb, but was decreased by carbaryl plus S‐9 in concentrations of > 40 ppm. In limb cultures, carbaryl without S‐9 was significantly toxic at 8–25 ppm, but only concentrations of > 25 ppm of carbaryl plus S‐9 significantly affected cytotoxicity. In contrast, aldicarb without S‐9 caused no effect on limb cell cytotoxicity at concentrations of 40–200 ppm, but aldicarb plus S‐9 significantly reduced cellular cytotoxicity at concentrations of > 160 ppm. Carbaryl ± S‐9 decreased the spread of both brain and limb colonies; aldicarb ± S‐9 caused a significant increase in the spread of the brain but not limb colonies. These results suggest that toxicities of carbaryl and aldicarb can be detected in vitro, but that these two carbamates have a selective toxicity, with carbaryl toxic to both brain and limb buds and aldicarb more toxic to brain than limb cells. S‐9 was more likely to decrease the toxicity of carbaryl than the toxicity of aldicarb.
Incidence of residual levels of organophosphorus insecticides in farm produce in the region of murcia, spain. comparison of intake in the 1985–86 and 1989 campaigns
Authors: García S. Navarro , Cámara M. A. , Barba A. , Toledano R. , Luna A. 
Published: October 2006

AbstractWe calculated the effective dietary exposure to 20 organophosphorus insecticides in a sample of residents of the Region of Murcia (Spain). Calculations were based on the contamination of 2310 specimens of citrus fruits, pitted and seedy fruits and vegetables collected in the 1985–86 and 1989 campaigns. A comparison of the results from the two campaigns showed that the mean annual insecticide ingestion determined from the mean consumption of each type of farm produce fell from 7.82 mg to 5.55 mg over the 4‐year period studied. The total annual ingestion of insecticides during the 1985–86 and 1989 campaigns was ca. 0.133 and 0.1 mg kg−1 body weight; these values are well below the admissible annual ingestion of 29.565 mg kg−1 body weight.
Relationship between eye and skin irritation in rabbits using a series of textile fiber finishes
Authors: Kennedy Gerald L. , Banerjee Asit K. 
Published: October 2006

AbstractA series of 76 fiber finishes, typically composed of blends of lubricants, emulsifiers, antistatic agents and fatty acid soaps, were tested in rabbits to determine both the eye and the skin irritation potential. Each finish was classified as being either non‐, slightly, mildly, moderately or severely irritating to the target tissue during a 48‐h post‐treatment period. Seven (9.2%) of the finishes tested were severely irritating to both the skin and the eye; two (2.6%) were determined to be non‐irritating to both tissues. While occasionally finishes produced equal degrees of damage resulting in similar irritancy classifications, seven (9.2%) finishes were found to be severely irritating to the skin without producing any irritation in the eye. Conversely, one finish was found to be a severe eye irritant without producing any skin irritation. The suggested use of the skin irritation data to predict the ocular reaction needs to be carefully examined, particularly with materials such as these fiber finishes. The prediction that a severe skin irritant is also a severe eye irritant was demonstrated to be in error with 8 of 75 (10.5%) of the finishes studied. Further, there is little predictive association between the skin and eye irritation for these compounds.
Attempted use of zinc in vivo to protect against nitrogen mustard toxicity in tumor‐free and in l1210 leukemia‐bearing female b6d2f1 mice
Authors: Shackelford Mary E. , Tobey Robert A. 
Published: October 2006

AbstractThe use of alkylating agents in treating cancer is limited by their toxicity to both normal and tumor tissue. Early in vitro studies indicated that zinc might be effective in mitigating this toxicity to normal tissue. The present studies were done to determine the capability of zinc to induce in vivo a protective response to an alkylating agent without also contributing to mortality. Tumor‐free and L1210 leukemia‐bearing female B6D2F1 mice were treated with zinc before administration of the alkylating agent nitrogen mustard. Protocols for administration route and frequency as well as the chemical formulation of the zinc were varied. The effect of a phytate‐free diet was studied. Two parameters were used to determine the effectiveness of zinc in protecting animals from the toxicity of nitrogen mustard: the number of tumor‐free mice that survived and an increase in the median life span of the tumor‐bearing mice. The zinc‐induction protocols used in these studies provided a limited degree of protection against nitrogen mustard toxicity in tumor‐free female mice, but in tumor‐bearing animals the protective response elicited with the protocols examined did not provide an appreciable therapeutic benefit.
Acute hepatic and renal toxicity of dichlorobenzene isomers in fischer 344 rats
Authors: Valentovic Monica A. , Ball John G. , Anestis Dianne , Madan Elio 
Published: October 2006

AbstractStudies were conducted to examine acute hepatic and renal toxicity of dichlorobenzene (DCB) structural isomers. Male Fischer 344 (F344) rats were injected with 2, 3 or 4 mmol kg−1 of 1,2‐DCB, 1,3‐DCB or 1,4‐DCB (o−, m−, p−). Pair‐fed control (PFC) animals were injected (i.p.) with corn oil (1 ml kg−1). Hepatic and renal toxicity was quantitated 24 h after injection of DCB or vehicle. Plasma transaminase (ALT/GPT) activity was increased (P<0.05) by 1,2‐DCB as a function of dose administered. Centrilobular necrosis was observed in rats treated with 1,2‐DCB while morphology was relatively normal in rats treated with m‐ or p‐DCB. Administration of (2 or 4 mmol kg−1) 1,3‐DCB or 1,4‐DCB did not alter kidney weight or blood urea nitrogen (BUN) levels. Renal cortical slice accumulation of p‐aminohippurate (PAH) was decreased (P<0.05) by (2 and 4 mmol kg−1) 1,3‐DCB and (3 and 4 mmol kg−1) 1,2‐DCB while accumulation of the cation tetraethylammonium (TEA) was decreased by 4 mmol kg−1 1,4‐DCB. (TEA). The results of these studies demonstrated that ortho substitution enhanced hepatic and renal toxicity. The results also would suggest that the liver was more sensitive than the kidney for DCB toxicity.
Influence of methylamine and N,N'‐dimethylurea, the hydrolysis products of methyl isocyanate, on its systemic toxicity
Authors: Jeevaratnam K. , Sugendran K. , Vaidyanathan C. S. 
Published: October 2006

AbstractSubcutaneous administration of the LD50 dose of methyl isocyanate (MIC) to rats induced severe hyperglycaemia, lactic acidosis and uraemia in rats. Neither methylamine (MA) nor N,N′‐dimethylurea (DMU), the hydrolysis products of MIC, administered in equimolar doses had any influence on these parameters except for a marginal transient increase in plasma urea by DMU. Methyl isocyanate administration led to haemoconcentration, resulting in an increase in the plasma concentration of total proteins and a decrease in both the plasma concentration of albumin and the plasma cholinesterase activity. The hydrolysis products of MIC had no influence on any of these parameters. Thus, it seems reasonable to suggest that the systemic effects of MIC are caused by MIC per se, in spite of its high hydrolytic instability.
Partial contribution of biliary metabolites to nephrotoxicity, renal content and excretion of [14C]hexachloro‐1,3‐butadiene in rats
Authors: Payan J. P. , Beydon D. , Fabry J. P. , Morei G. , Brondeau M. T. , Ban M. , de Ceaurriz J. 
Published: October 2006

AbstractMale Sprague Dawley rats with cannulated bile duct (BDC rats) received 100 or 200 mg kg−1 labelled hexachloro‐1,3‐butadiene ([14C]HCBD) by gavage 1 h (BDC1, rats) or 24 h (BDC24 rats) after surgical cannula implantation. Twenty‐four hours after treatment with HCBD, rats were examined histochemically and biochemically for kidney damage. Urine, faeces, liver and kidney radioactivities were also measured in 24‐h samples. Results were compared with those obtained from non‐cannulated (NC) rats. Bile‐duct cannulation did not completely protect against HCBD‐induced kidney damage. The 24‐h [14C] urinary excretion and tissue content was 30–50% lower in BDC rats compared to NC rats and correlated well with the toxicity findings.BDC1 rats appeared to be much more resistant to HCBD treatment than BDC24 rats. Since faecal [14C] radioactivity extractible by diethyl ether at neutral pH in BDC1, rats was twice that measured in BDC24 rats, the greater resistance was attributed to a higher deficiency in the gastrointestinal absorption of unchanged HCBD.The present results reveal that the biliary metabolites of HCBD are not solely responsible for kidney toxicity as previously assumed. They suggest a sinusoidal efflux of the HCBD conjugates from the liver.
The dermal bioavailability of radiolabelled benzo[a]pyrene from acetone or from oils of differing viscosity, assessed by DNA and protein binding
Authors: Ingram A. J. , Phillips J. C. 
Published: October 2006

AbstractTritium‐labelled benzo[a]pyrene ([3H]BaP) was applied to mouse skin in acetone or mineral oils of differing viscosity. Epidermal DNA and protein were extracted after 24 or 48 h and the degree of adduct formation determined by the radioactivity present.When [3H]BaP was applied in acetone, the degree of DNA and protein binding was around 15–20 times greater than that observed when a low‐viscosity oil was used as a vehicle. When applied in oils of differing viscosity, however, only a twofold difference was seen across the whole viscosity range (13.5 cStSt = stokes, a unit of kinematic viscosity (10−4 m2 s−1)
at 40°C to 1665 cSt at 60°C). From measurements made of urine and fecal radioactivity and from small‐scale investigations using other routes of administration, it was clear that the grooming activity of the animals had a marked effect on skin absorption and macromolecular binding. It is possible that greater grooming activity with low‐viscosity oils may explain why oil viscosity did not have a greater effect on binding levels, but further studies are needed to investigate this.These findings may have important implications in the interpretation of long‐term skin painting studies and may assist in the interpretation of analytical data and short‐term biological assays.
Alterations in hepatic biochemistry of mice intoxicated with MIC, carbaryl and thiram
Authors: Gupta Meenakshi , Amma M. K. P. 
Published: October 2006

AbstractThe effect of different doses of methyl isocyanate (MIC), carbaryl and thiram on liver microsomal mixed‐function oxygenases (MFO) was studied in adult Swiss Portan mice by intraperitoneal (i.p.) injection for different durations. The LD50 dose of all three toxicants after 0.75 h of administration could increase cytochrome P‐450 and cytochrome b5 contents (82–143%), and the 1/4LD50 of these compounds could elicit the same effect after 168 h (168–393%). The 1/4LD50 dose of thiram decreased the cytochrome P‐450 content below the control level (69.62%) in 0.75 h and the same dose of MIC could decrease the cytochrome P‐450 level by 40% compared to the control after 3 days of consecutive injection. The activities of drug‐metabolizing enzymes (aminopyrine demethylase—NADH and NADPH‐linked—and aniline hydroxylase) were found to increase with all three compounds in general. Marked changes in the activity of the marker enzyme glucose‐6‐phosphatase were also seen after i.p. injection if MIC, carbaryl and thiram. These findings suggested that these compounds were hepatotoxic, which could be due to their carbamylating nature.