bluuebunny/crossref_metadata_2025_split huggingface dataset:
The combined effect of Pb2+ and Mn2+ on monoamine uptake and Na+, K+‐ATPase in striatal synaptosomes
Authors: Hussain Tahir , Ali M. M. , Chandra S. V. 
Published: October 2006

AbstractRat striatal synaptosomes (P2‐fraction) were subjected to lipoperoxidation by the addition of 120 μM Fe2+ and 200 μM ascorbic acid. This preparation (pretreated synaptosomes) was used to investigate the interaction of Pb2+ and Mn2+ on the uptake of tritiated catecholamines, Na+, K+‐ATPase activity and malondialdehyde (MDA) formation in order to understand the mechanism of enhanced neurotoxocity by concurrent exposure to these metals. The combination of Pb2+ and Mn2+ (25 μM + 100 μM, respectively) produced a significant increase in the uptake of 3H‐Dopamine only in the untreated synaptosomes. No significant effect was noted on the uptake of 3H‐Norepinephrine in either pretreated or untreated synaptosomes. However, the combination of Pb2+ and Mn2+ produced a pronounced decrease in the activity of Na+, K+‐ATPase, but the magnitude of the change was the sum of the individual metal effects. Metal interaction did not produce any significant change in the formation of MDA compared to the control (without addition of metals). These results indicate that Pb2+ and Mn2+ interaction may produce inhibition in the activity of transport ATPase in both the preparation of synaptosomes, with more pronounced effect of synaptosomes subjected to lipoperoxidation and these changes may be responsible for the disruption in the physiology of nerve impulse transmission.
Nuclear enlargement produced in mouse skin by carcinogenic mineral oils
Authors: Ingram A. J. , Grasso P. 
Published: October 2006

AbstractTen oils of differing origin, degree of refinement and carcinogenicity, were examined for their ability to produce nuclear enlargement in mouse skin following repeated topical exposure over a 3 day period. Application of the oils was made in a vehicle of methyl ethyl ketone incorporating a promoter and assessment of epidermal nuclear size was made on tissue sections using a Quantimet 720 image analyser.One of the oils reported to be non‐carcinogenic; was examined initially and its inability to induce enlargement of nuclei beyond the size seen in hyperplastic skin was confirmed. The same oil was then examined in combination with benzo(a)pyrene (BaP) and, from the dose–response obtained, it was clear that the oil did not prevent BaP induced nuclear enlargement.The other nine oils were examined by comparing them with the previously tested non‐carcinogenic oil. Two oils gave rise to clear nuclear enlargement; these were non‐solvent refined and gave rise to skin tumours in reported long‐term studies. One solvent‐refined oil, which gave a single papilloma in reported long‐term studies, gave borderline (non‐significant) nuclear enlargement; whereas the other solvent‐refined oils, including five reported as non‐carcinogenic and one reported as having weak (questionable) carcinogenic activity, gave no nuclear enlargement.Further examination of the data suggested that, within the limited series of oils examined, nuclear enlargement under these test conditions correlated well with carcinogenicity and might be used for predicting the skin carcinogenicity of an oil. Studies on a further 23 oils, on which long‐term studies have been carried out but not published, support this conclusion.
Developmental toxicity studies of caprolactam in the rat and rabbit
Authors: Gad Shayne C. , Robinson Keith , Serota David G. , Colpean Barbara R. 
Published: October 2006

AbstractCaprolactam was evaluated for developmental toxicity potential in both rats and rabbits by the oral route. In rats dosed on days 6–15 of gestation with 100, 500 or 1000 mg/kg/day of caprolactam, the maternal survival rate was significantly lower in the high‐dose group and implantation efficiencies were slightly lower in the 100 and 1000 mg/groups (but not the 500 mg/kg) than in the control. The incidence of fetal death was comparable for all groups, and the incidence of fetal viability was considerably lower in the high‐dose group (but not the mid or low) than in the control group. Visceral anomalies and one visceral variant were observed in one 100 mg/kg and one 500 mg/kg pup, respectively. The anomalies included exencephaly, an incomplete left eyelid, microphthalmia (right), and a protruding tongue. No skeletal anomalies were observed. It was concluded that caprolactam at levels up to at least 500 mg/kg of body weight produced no teratogenic effects in the Fischer 344 rats.In rabbits receiving 50, 150 or 250 mg/kg caprolactam on days 6–28 of gestation, the pregnancy rate in all groups was at least 80%. The numbers of corpora lutea, live and dead fetuses, resorptions, the sex ratio and the pre‐ and post‐implantation losses were not significantly different among the test and control groans. The incidence of major malformations and of minor skeletal anomalies was unaffected by treatment with caprolactam. Maternal weights were depressed in the group receiving 250 mg/kg. Treatment of a separate group with a positive control substance (ó‐aminonicotinamide) resulted in significantly (P < 0.001) increased incidences of major malformations, minor visceral anomalies and minor skeletal anomalies. Maternal toxicity in terms of mortality was observed in pregnant rabbits treated with caprolactam at a dose of 250 mg/kg/day. Fetotoxicity was evidenced by lower fetal weights at the 150 and 250 mg/kg/day levels, and an increased incidence of thirteenth ribs was observed at the 250 mg/kg/day dose level. Neither embryotoxicity nor teratogenicity occurred at any dose level.
Decision criteria for the in vitro rat hepatocyte UDS assay
Authors: Oshiro Y. , Balwierz P. S. , Falk R. W. , Piper C. E. 
Published: October 2006

AbstractThe induction of unscheduled DNA synthesis (UDS) in rat primary hepatocytes is used as an in vitro screen for genotoxicity. The purpose of this study was to develop criteria for statistical evaluation of autoradiographic grain counts from the UDS assay. Based on our historical solvent control population (N = 17), we first established a predictive two‐sided symmetric tolerance interval providing 95% confidence for coverage of 99% of the distribution of the mean net nuclear grain count for a new solvent control observation. The tolerance interval was determined to run from −2.82 to 4.03 net nuclear grains. When the concurrent solvent control (C) proves admissible (−2.82 < C < 4.03), the mean net nuclear grain counts from treatment groups are compared to the concurrent solvent control value. If the difference exceeds 3.09 at two successive concentrations, the test compound is considered positive. We have tested eight carcinogens (MNNG, AFB1, 4DAB, 4NQO, DMBA, 2AAF, DEN and 2AA) utilizing these criteria. All eight were positive. Four non‐carcinogens (2AB, pyrene, anthracene and αNA) were negative. Each of these chemicals was tested twice using our standard protocol, which employs a preliminary range‐finding cytotoxicity assay. We conclude that these criteria provide adequate sensitivity and specificity to be applicable for the evaluation of the results of routine UDS assays with compounds of unknown genotoxic potential.
Alterations in urethan‐induced adenoma formation in mice exposed to selenium and nickel
Authors: Blakley Barry R. 
Published: October 2006

AbstractFemale Swiss mice were exposed to sodium selenite (3 μ/ml selenium content) and nickelous chloride (100 μg/ml nickel content) in the drinking water on alternate days for 15 weeks. After 3 weeks of metal exposure, the mice were administered urethan (1.5 mg/g) intraperitoneally. Pulmonary adenoma formation was evaluated 12 weeks later. Selenium exposure did not alter the tumor incidence (P = 0.059) or the tumour size (P = 0.98). Nickel exposure did not affect the tumour incidence (P = 0.25), but increased the average tumour size (P = 0.0025). Combined selenium and nickel exposure resulted in significant interactions associated with tumour size (P = 0.00075) and tumour number (P = 0.045). Urethan‐induced sleeping times were reduced by selenium exposure (P = 0.0049), but were unaffected by nickel exposure (P = 0.99). Combined metal exposure did not influence urethan‐induced sleeping times (P = 0.48).
Hepatotoxic effects elicited by n‐hexane or n‐ heptane
Authors: Goel S. K. , Rao G. S. , Pandya K. P. 
Published: October 2006

AbstractHepatotoxic effects of n‐hexane and n‐heptane administered i.p. (1 ml/kg body wt) were studied in albino rats after 1, 2, 7 and 45 days of treatment. Hepatic protein content decreased with n‐heptane and total sulphydryl content showed a significant decrease in the rats exposed to either solvent. A significant increase in lipid peroxidation was observed after 24 h and 48 h exposure to n‐hexane or n‐heptane. A marked decrease in drug metabolizing activity and an increase in pentabarbitone sleeping time was also observed. Hepatic glucose‐6‐phosphatase, a microsomal marker enzyme, showed a significant decrease.
Effects of nitrosation on the chemical composition and epidermal carcinogenicity of the nitrogen‐rich fraction of a high‐boiling coal liquid
Authors: Wright C. W. , Chess E. K. , Renne R. A. , Buschbom R. L. 
Published: October 2006

AbstractAn 800–850°F solvent‐refined coal‐II liquid was fractionated into chemical classes to obtain the aliphatic hydrocarbons, polycyclic aromatic hydrocarbons (PAH), nitrogen‐containing polycyclic aromatic compounds (NPAC), and hydroxy‐subsituted PAH (hydroxy‐PAH). The isolated NPAC fraction was refractionated by chemical class both before and after undergoing a nitrosation reaction. The nitrosated and non‐nitrosated refractionated NPAC fractions were further subfractionated into secondary amine (pyrroles), primary amine‐enriched (amino‐PAH), and tertiary amine (azaarene) classes. The PAH and hydroxy‐PAH composition of the NPAC fraction increased upon nitrosation, whereas the amino‐PAH fraction composition decreased upon nitrosation. Nitrosation of standards indicated the amino‐PAH compounds reacted to form parent PAH, chloro‐substituted PAH, and methoxy‐substituted PAH when analyzed by high‐resolution gas chromatography (GC) and GC/mass spectrometry (MS). Some easily oxidized PAH compounds reacted to form ketones and quinones. All other standard reference compounds, chosen to be representative of the major chemical classes of compounds present in coal liquefaction materials, were unchanged by the nitrosation reaction. The amino‐PAH of the nitrosated NPAC fraction reacted to form parent and some chloro‐substituted PAH when analyzed by low‐voltage direct‐probe MS in addition to the methods given above. Epidermal carcinogenesis studies with the PAH, NPAC, nitrosated NPAC, and hydroxy‐PAH fractions isolated from the 800–850°F coal liquid indicated the PAH and NPAC were the most important determiners of skin carcinogenesis, with the PAH giving a higher response than the NPAC. The tumorigenicity of the NPAC was drastically reduced by nitrosation, probably due to the destruction of the amino‐PAH upon nitrosation.
Cellular metabolism of arsenocholine
Authors: Christakopoulos Alexandros , Norin Harald , Sandström Margareta , Thor Hjördis , Moldeus Peter , Ryhage Ragnar 
Published: October 2006

AbstractThe biotransformation of arsenocholine and arsenobetaine, which are organic arsenic compounds present in certain aquatic organisms, has been studied in vitro using synthetic reference substances. Incubation of arsenocholine with different liver cell fractions showed arsenocholine to be biotransformed only in presence of the mitochondrial fraction. The biotransformation products were arsenobetaine aldehyde, arsenobetaine, trimethylarsine oxide and trimethylarsine. Arsenobetaine was the major metabolite and it was formed via arsenobetaine aldehyde. Trimethylarsine oxide was formed via a side reaction from arsenobetaine aldehyde. Further reduction of trimethylarsine oxide, produced trimethylarsine. In vitro studies of arsenobetaine, did not show any formation of trimethylarsine oxide or trimethylarsine. Furthermore, cytotoxicity of arsenobetaine or arsenocholine in isolated hepatocytes was not observed.
In vitro mutagenicity of water contaminants in complex mixtures
Authors: Varma M. M. , Ampy F. R. , Verma K. , Talbot W. W. 
Published: October 2006

AbstractTrihalomethanes, Carbon tetrachloride and trichloroethylene were tested in single, binary and multi‐complex mixtures using standard tester strains TA1535, TA1537, TA98 and TA100 of Salmonella typhimurium with and without addition of an in vitro metabolizing fraction S‐9. Chloroform (CHCl3) was found to be mutagenic in all strains without S‐9 activation. However, when tested with Bromoform (15%), which was nonmutagenic singly, the combined effect of the mixture was nonmutagenic. CCl4 was a direct mutagen (without S‐9) in all strains except TA 1535. When combined with 85% CHCl3, only strains TA1535 and TA1537 were mutagenic. When tested with mammalian activation (S‐9), CCl4 was mutagenic in all strains. However, when tested with CHCl3 (CHCl3 and CCl4 ‐ 85 : 15), the mutagenic capability was lost.With or without S‐9 Activation multi‐complex mixture of CHCl3, CCl4 and TCE (85 : 8 : 7) was mutagenic for a narrow range of doses in all strains.
Tris (2,3‐dibromopropyl) phosphate nephrotoxicity in the rat: Histological and biochemical changes in renal components by 13C‐NMR spectra
Authors: Fukuoka Masamichi , Tanaka Akira , Yamaha Tsutomu , Naito Katushi , Takada Koichi , Kobayashi Kazuo , Tobe Masuo 
Published: October 2006

AbstractRats receiving a single oral dose of 286.8 μmol/kg tris(2,3‐dibromopropyl)phosphate (Tris‐BP) showed pyknosis of the renal tubular epithelial cells on Day 1, necrosis on Day 2, regeneration from Day 3 and large nuclei formation from Day 4. 13C‐NMR spectra were applied to clarify changes of the renal low‐molecular‐weight components in the kidney injured by Tris‐BP, and sialic acid and inositol were found as the desired marker components. The lesions produced by Tris‐BP were characterized by changes in the renal components and enzyme activities. Increases in sialic acid content of the kidney were observed both on Day 1, suggesting destruction of the epithelial cell membrane, and on Day 5, suggesting regeneration accompanied by an increase of inositol content on Days 7 and 10. Renal activity of cytoplasmic enzyme, alanine aminopeptidase, was decreased on Days 1 and 5 and elevated on Days 7 and 10. Lactate dehydrogenase activity showed a tendency to decrease in the kidneys on Day 1 and to increase significantly on Days 2, 5, 6 and 7.
Evidence that phomopsins A and B are not the only toxic metabolites produced by Phomopsis leptostromiformis
Authors: Allen J. G. , Hancock G. R. 
Published: October 2006

AbstractThe toxicities of up to four different toxic preparations containing metabolites of Phomopsis leptostromiformis were examined in two experiments with sheep and one with rats. It was shown that the different toxic preparations containing similar amounts of phomopsin A varied substantially in toxicity. Crystalline phomopsin A was the least toxic. It is suggested that the increased toxicity of the other three preparations was due to the presence of toxic metabolites additional to phomopsins A and B. Evidence to support this suggestion is presented.
The histochemical location of three diagnostic enzymes in the marmoset liver
Authors: Davy C. W. , Fulleylove M. , Edmunds J. , Allsop D. , Eichler D. A. , Rushton B. , Walker J. M. 
Published: October 2006

AbstractThe histochemical locations of alkaline phosphate (ALP), leucine aminopeptidase (LAP) and gamma glutamyl‐transferase (GGT) were demonstrated in the liver of the marmoset (Callithrix jacchus). Although all three enzymes were located in cell membranes, the location of LAP was demonstrated by a chromogenic substrate, in the canalicular membrane. GGT was seen in a vascular network, provisionally identified as the peribiliary arterial plexus. Possible diagnostic applications in toxicology are discussed.
Toxicity of aromatic thiols in the human red blood cell
Authors: Amrolia Persis , Sullivan Stephen Gene , Stern Arnold , Munday Rex 
Published: October 2006

AbstractThiophenol and 4‐aminothiophenol were used to study levels of toxicity in human red blood cells. Thiophenols caused conversion of oxyhemoglobin to methemoglobin. Reduction of corresponding disulfides by intracelluar glutathione caused cyclic reduction/oxidation reactions, resulting in increased oxidative flux. Three levels of oxidative stress were observed in these experiments: the lowest level resulted from incubation with 0.25 mM thiophenol; the intermediate level with 0.50 mM thiophenol or 0.25 mM 4‐aminothiophenol; the highest levels with 0.50 mM 4‐aminothiophenol. Methemoglobin formation increased with increasing level of oxidative stress. Glycolysis and the hexose monophosphate shunt were inhibited at the intermediate and highest levels of stress, respectively. Above the highest level of stress non‐intact hemoglobin was formed and cell lysis occurred. These metabolic responses were reflected in cellular levels of NADH, NADPH and reduced glutathione. At the lowest level of oxidative stress, both glycolysis and hexose monophosphate shunt were increased such that near‐normal levels of NADH, NADPH and reduced glutathione were maintained and methemoglobin formation was kept to a minimum. The response of red cells to 0.25 mM thiophenol appears to represent a level of oxidative stress to which the cell is capable of adaptive metabolic response. Glycolysis contributes approximately one‐quarter of the total reducing equivalents from glucose metabolism in response to the oxidative challenge by thiophenol. The results suggest that the metabolic response to autoxidation of endogenous thiols is thiol exchange with glutathione and reduction of resulting glutathione disulfide by the hexose monophosphate shunt.
Renal and hepatic toxicity of N‐arylsuccinimides in fischer 344 rats
Authors: Rankin Gary O. , Carl John M. , Hubbard John L. , Teets Vonda J. , Nicoll Derek W. , Brown Patrick I. 
Published: October 2006

AbstractThe role of aromaticity in the nephrotoxic potential of N‐arylsuccinimides was studied in male Fischer 344 rats. Rats were administered a single intraperitoneal (i.p.) injection of an N‐arylsuccinimide derivative (0.4 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg), and the renal function monitored at 24 and 48 h. The parent compound in this series, N‐phenylsuccinimide (NPS), had previously been shown to induce only minimal renal effects, having no effect on urine volume, blood urea nitrogen concentration, kidney weight, p‐aminohippurate accumulation or renal morphology. Only an increase in tetraethylammonium uptake has been observed following NPS administration to rats. These effects were not enhanced by reducing aromaticity (N‐cyclohexylsuccinimide (NCS)). Compounds with increased aromaticity N‐(1‐naphthyl)succinimide (NNS), N‐(1‐anthracenyl)succinimide (1‐NAS) and N‐(9‐anthracenyl)succinimide (9‐NAS) — also only weakly affected renal function. However, NNS (1.0 mmol/kg) and, to a lesser degree, 9‐NAS (1.0 mmol/kg) proved to be hepatotoxins. Liver damage was most pronounced near central vein regions of the lobule and least evident around periportal sites. Damaged liver tissue exhibited unusually large deposits of connective tissue and hypertrophied hepatocytes with numerous vacuoles in their cytoplasm. Therefore, derivatives of NPS with increased or decreased aromaticity relative to the parent compound do not exhibit the ability to induce moderate or marked nephrotoxicity. However, increasing aromaticity did produce the derivatives NNS and 9‐NAS, which are hepatotoxins. These compounds represent the first members in this series of compounds to induce acute hepatotoxicity.
A new method for long‐term inhalation toxicity studies for bronchospasmolytic aerosol formulations in dogs
Authors: Pauluhn Jürgen , Kimmerle Georg 
Published: October 2006

AbstractIn routine inhalation toxicity studies laboratory animals are exposed under dynamic exposure conditions to different steady‐state concentrations of a test compound. The relevant exposure concentration is the analytically determined time‐weighted average concentration in the vicinity of the breathing zone of the animals. If the intended use of a bronchospasmolytic aerosol is taken into account, a non‐steady‐state exposure regimen might be more appropriate. Using this approach local effects of high aerosol concentrations on the respiratory tract were investigated in dogs by daily head/nose‐only exposure for 1 h for 4 weeks. Four groups of four dogs were exposed to 20, 40 and 80 bursts of a bronchodilator formulation using a modified metered dose inhaler. The analytically determined mean concentration of the active ingredient (prostaglandin) in the breathing zone was 43.1, 92.2 and 193.9 μg 𝓁−1 air, respectively. Maximum concentrations were determined by simulation. The aerosol was in the respirable range (mass median aerodynamic diameter ∼ 1.2 μm, geometric standard deviation ∼ 1.4).A kinetic model was developed to simulate the mean and maximum non‐steady‐state concentration for an exposure regimen of 20, 40 and 80 bursts per hour under dynamic exposure conditions. The model was based on first‐order inhalation chamber kinetics. The kinetic model was validated experimentally by comparing measured mean and simulated mean concentrations. In all exposure groups the simulated maximum concentrations were ca. 80 mg of test compound (formulation) per litre of air. Plasma levels were elevated in a dose‐dependent manner as evidence of the validity of the test model employed.
The dermal carcinogenic potential of unrefined and hydrotreated lubricating oils
Authors: McKee R. H. , Daughtrey W. C. , Freeman J. J. , Federici T. M. , Phillips R. D. , Plutnick R. T. 
Published: October 2006

AbstractUnrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method.The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyree), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice‐weekly aliquots to the backs of 40 male C3H mice.In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non‐carcinogenic products.