bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 13‐week vapor inhalation study of 3,3‐dimethyl‐2‐butanol in sprague‐dawley rats
Authors: James John T. , Armstrong Robert D. , Leach Glenn , Farrand Richard L. , Burnett David , Englee Mae Jean , Hall William C. 
Published: October 2006

AbstractFour groups of male and female Sprague‐Dawley rats were exposed for 13 weeks to 3,3‐dimethyl‐2‐butanol (PA) at concentrations of 0.00, 0.20, 1.00 or 5.00 mg/l (1 mg/l = 240 ppm). Exposures were for 6 hr per day, 5 days per week with sacrifices at 7 and 13 weeks of exposure, and at 4 weeks after exposure. The test animals were evaluated for abnormalities in physiology, behaviour, clinical laboratory parameters, and gross and microscopic morphology. No abnormalities were detected in electrocardiograms, respiratory indices, spontaneous activity, passive avoidance activity and open‐field behaviour. Clinical signs related to PA exposure included alopecia, ataxia and lacrimation. There were no biologically significant between‐group differences in body‐weights during the study. The clinical laboratory data demonstrated a 30% increase in serum cholesterol and bilirubin at 7 weeks in high‐dose males and an increase in urea nitrogen in intermediate and high‐dose males at 13 weeks. There were no abnormalities in hematologic or coagulation parameters. At necropsy there were no significant gross abnormalities; however, examination of organ weights revealed enlarged kidneys in high‐dose male rats at 13 weeks, enlarged ovaries in high‐dose female rats at 13 weeks, and microscopic study of tissue sections revealed minimal to mild renal tubular injury in high and possibly intermediate dose males at several sacrifices.These findings suggest that the primary target organ of PA, when given by inhalation, is the kidney in male rats and possibly the ovary in female rats. The renal changes in the high‐dose males were not fully reversible during the recovery period. Because abnormalities were also observed in the intermediate‐dose males, the no‐observed‐effect level is 0.2 mg/I. The renal lesions were morphologically similar to those reported in male rats exposed to hydrocarbons and may be unique to male rats. It must be emphasized that PA, like most alcohols, is not highly toxic by the inhalation route.
Sensory irritation of methylisocyanate vapor
Authors: James John T. , Buettner Leonard C. , Hsu Sam S. 
Published: October 2006

AbstractThe respiratory‐depression (RD) profile in mice exposed to methylisocyanate (MIC) vapor is reported. The RD50 value calculated from this profile was 2.9 (2.7–3.2) ppm. Concentrations of MIC that have been reported to be unbearable in humans were of approximately the same magnitude as RD50 concentrations in mice for brief exposures.
Comparative studies on nephrotoxic effects of Tris (2,3‐dibromopropyl) phosphate and Bis (2,3‐dibromopropyl) phosphate on rat urinary metabolites
Authors: Fukuoka Masamichi , Takahashi Terue , Naito Katsushi , Takada Koichi 
Published: October 2006

AbstractThe mechanism of Tris‐BP or Bis‐BP (a metabolite of Tris‐BP) induced nephrotoxicity was investigated by determining urinary excretion of enzymes and selected metabolites. Rats received single oral doses of 0, 71.7, 143.4 and 286.8 μmol/kg tris (2,3‐dibromopropyl) phosphate (Tris‐BP) or bis (2,3‐dibromopropyl) phosphate (Bis‐BP). Urine was collected over a 24 h period and subjected to biochemical examinations. Comparative studies on Tris‐BP‐ and Bis‐BP‐induced nephrotoxicities were carried out for abnormal patterns of urinary excretion. The urinary excretion of glucose was higher in Bis‐BP than Tris‐BP at a dose of 143.4 μmol/kg, but this pattern reversed at a dose of 286.8 μmol/kg. Peak lactate excretion occurred later than peak glucose excretion with 143.4 and 286.8 μmol/kg Tris BP and 143.4 μmol/kg Bis‐BP. Bis‐BP 286.8 μmol/kg caused a transient urinary elevation of lactate on Day 2. Uric acid was excreted at higher levels for Bis‐BP than Tris‐BP on day 2 of urine collection. Activities of urinary enzymes including alkaline phosphatase, aspartate aminotransferase and γ‐glutamyltransferase, were different on the first day of post‐treatment for Tris‐BP and Bis‐BP. Leucine aminopeptidase and lactate dehydrogenase levels differed on the second day. Activities of the former enzymes on the day 2 urine suggested a transformation of Tris‐BP to Bis‐BP. Urinary patterns of lactate dehydrogenase isoenzymes (LDH‐1‐LDH‐5) were different between Tris‐BP and Bis‐BP when rats were treated with the dose of 286.8 μmol/kg: Tris‐BP caused a higher excretion of LDH‐4 and LDH‐5 in urine on day 1 and all five isoenzymes into the day 2 urine. Bis‐BP caused slightly higher excretion of LDH‐5 and LDH‐4 into the day 1 and 3 urine, respectively. Bis‐BP but not Tris‐BP caused abnormally urinary excretion of sodium ion. Histopathologically, the nephrotoxic effect of Tris‐BP appeared one day later and was more obvious than that of Bis‐BP in rats after single oral administration.
Comparative sensitivity of histo‐pathology and specific lung parameters in the detection of lung injury
Authors: Hooftman R. N. , Kuper C. F. , Appelman L. M. 
Published: October 2006

AbstractThe sensitivity of different parameters for the determination of lung injury caused by nitrogen dioxide (NO2) was investigated. Male rats were exposed to concentrations of 0, 4, 10 or 25 ppm NO2 for 6 h/day, for 7, 14 or 21 days. Histopathology of the nasal cavity, larynx, trachea and lungs was compared with the changes in macrophage function and morphology. In addition several biochemical parameters were determined in lung lavages. Cytotoxic effects were investigated in primary cultures of rat and bovine alveolar macrophages, exposed to the same NO2‐levels as in the in vivo exposure. Treatment‐related histopathological changes were observed in the lungs. No differences between exposed and control animals were observed in the nasal cavity, larynx or trachea. The morphology of the lavaged alveolar macrophages was changed at all exposure concentrations on day 7, 14 and 21. An increase in the number of macrophages was found after exposure to 10 and 25 ppm NO2 on days 7, 14 and 21. The phagocytic capacity was diminished after 14 and 21 days exposure to 25 ppm and at both times exposure to 10 and 25 ppm increased the level of gamma‐glutamyl transferase (GGT) in lavage fluids. Morphology of the macrophages and levels of GGT were found to be sensitive parameters of nitrogen dioxide toxicity. In vitro exposure of rat and bovine alveolar macrophages to comparable NO2‐concentrations induced effects on phagocytosis similar to those observed for macrophages from exposed rats.
Nuclear aberrations and micronuclei induction in the digestive tract of mice treated with different iron salts
Authors: Bianchini F. , Caderni G. , Dolara P. , Tanganelli E. 
Published: October 2006

AbstractToxic effects of ferrous sulfate and of ferric chloride were determined in the gastrointestinal tract by measuring the induction of nuclear aberrations and micronuclei. In fasting animals ferric chloride induced a dose‐related increase of nuclear aberrations in the stomach, whereas ferrous sulfate was not active. In normally feeding animals no increase of nuclear aberrations was observed. The effects of the iron compounds on the duodenum were minimal. In fasting animals a dose‐related increase of nuclear aberrations was observed at the level of the colon, with no clear difference between ferrous and ferric compounds. A modest increase of nuclear aberrations of the colon was seen in feeding animals only with ferrous sulphate. By intrarectal administration, nuclear aberrations were induced especially by ferric chloride.An increase of the frequency of micronuclei was not observed at the level of the stomach, duodenum and colon, with the exception of ferric chloride, that induces a significant, although small increase of colon micronuclei when administered intra‐rectally. The data demonstrate that iron compounds have an intrinsic cellular toxicity when not administered with food, but do not seem to carry any genotoxic potential for the gastrointestinal tract.
An illustration of dangers of ignoring survival differences in carcinogenic data
Authors: Bailer A. John , Portier Christopher J. 
Published: October 2006

AbstractThis paper illustrates the effects of survival differences on the routine analysis of 2‐year animal carcinogenesis experiments using quantal response. Not adjusting for decreased survival in the higher dosed groups results in a decrease in the actual significance level for the quantal response trend test, and a corresponding decrease in sensitivity for detecting a true treatment effect. Similar results hold for estimation of carcinogenic risk. Tables of the range of survival differences found in recent National Toxicology Program carcinogenesis studies are presented.
Oxmetidine (H2 receptor antagonist) induced cytotoxicity in isolated rat hepatocytes
Authors: Willson R. A. , Hall T. , Hart J. 
Published: October 2006

AbstractOxmetidine, a new and more potent analogue of the H2 receptor antagonist, cimetidine, was recently withdrawn from clinical trials because of associated hepatotoxicity. We investigated the potential hepatotoxicity of the drug in vitro and in vivo in the rat. In addition, we investigated, in in vitro experiments, the potential hepatoxicity of other gastric acid inhibitory drugs (cimetidine, ranitidine, omeprazole and nolinium bromide). In in vitro experiments, oxmetidine, at various concentrations, was added to isolated hepatocyte incubations and cytoxicity was assayed by trypan blue exclusion. In in vivo experiments, oxmetidine was administered both i.p. and orally, and hepatotoxicity was assessed by serum biochemical measures (transaminases, alkaline phosphatase, 5′nucleotidase, gamma glutamyl transpeptidase) and liver histopathology. In the in vitro studies, the addition of oxmetidine to the hepatocyte incubations was associated with significant (P<0.001) dose and time dependent cytotoxicity. However, the in vivo experiments revealed no significant changes in serum biochemistry and no significant alterations in liver histopathology up to 72 h following the administration three different dosages of oxmetidine. Of the other gastric acid inhibitory drugs, only nolinium bromide was associated with significant (P<0.001) in vitro cytotoxicity. Our in vitro observations establish that oxmetidine is cytotoxic to isolated rat hepatocytes and suggest that nolinium bromide be further evaluated for potential hepatotoxicity.
Uptake of inert particles by dog alveolar macrophages in vitro — a comparison of monolayer and suspension techniques
Authors: Mueller Heinz‐Leonhard , Guilmette Raymond A. , Muggenburg Bruce A. 
Published: October 2006

AbstractThis study was conducted to determine if significant differences in phagocytosis occurred in pulmonary alveolar macrophages in suspension or monolayer cultures. Dog alveolar macrophages were incubated with different numbers of fluorescent polystyrene latex microspheres, both in suspension and in monolayer cultures. The particle uptake by cells was linear for 10–100 min and the fraction of cells that contained particles was similar for both incubation techniques. Differences between carboxylated and non‐carboxylated microspheres were statistically not significant. The overall particle numbers associated with cells were 2–5 times higher for cells incubated in suspension compared to adherent cells. Many more cells were found with low particle numbers at all incubation times using the monolayer technique compared to the suspension technique. When cells were treated with xylene for 1 h after different times of incubation in vitro, a higher decrease in particle numbers in cells was found in suspension cultures than in monolayer cultures. This finding suggests higher particle binding when cells were incubated in suspension, but particle numbers after xylene treatment were still higher in cells incubated in suspension than in monolayers. A comparison with the uptake of similar particles by dog alveolar macrophages in vivo suggests that the suspension cultures were more similar to the events in the dog lung, but uptake rates were about a factor of two lower with suspended cells than those seen in vivo.
Role of activated oxygen species on the mutagenicity of benzo[a]pyrene
Authors: Wei C. E. , Allen K. , Misra H. P. 
Published: October 2006

AbstractDifferent scavengers of active oxygen species (superoxide dismutase, catalase, mannitol and dimethylfuran) were tested in the Ames Salmonella assay to determine the role of the reactive oxygen species in the benzo[a]pyrene (B[a]P) mutagenesis process. Exogenously added superoxide dismutase or catalase at 10–100 μg ml−1 top agar, or 3–12 mM mannitol showed no effect on B[a]P mutagenicity in the presence of S9 mix. However, dimethylfuran (DMF), a singlet oxygen scavenger, inhibited in a dose‐related manner the mutagenic response of B[a]P in the presence of the microsomal fraction. DMF at 3 and 6 mM inhibited the number of revertants by 69 and 93% for strain TA 100, and 76 and 78% for TA 98, respectively. DMF at these levels was neither toxic nor mutagenic to the bacteria. The result indicates that singlet oxygen may play an important role in promoting B[a]P mutagenicity.
Further evidence that dichloromethane does not induce chromosome damage
Authors: Westbrook‐Collins Barbara , Allen James W. , Sharief Yousuf , Campbell James 
Published: October 2006

AbstractDichloromethane (DCM) is a widely used industrial solvent that has been determined to be a carcinogen in rats and mice. In vitro and in vivo analyses of chromosome damage induced by this agent have provided conflicting results. In order to further investigate the clastogenic potential of DCM in vivo, we analyzed sister chromatid exchanges (SCEs) and chromosome aberrations (CAs) in mouse bone marrow cells following intraperitoneal exposures of 100–2000 mg kg−1 DCM. Dichloromethane failed to increase the frequencies of either SCEs or CAs.
Comparative flow cytometric analysis of bleomycin toxicity on normal and tumour sheep cell kinetics in vitro
Authors: Shrivastava Ravi , Ratinaud Marie Helene , Julien Raymond 
Published: October 2006

AbstractThe cytotoxic effects of bleomycin on cell proliferation, morphology and cycle progression were compared in a sheep tumour cell line and in normal sheep sinus cells. They were concentration and time dependent, irreversible, and were accompanied by increased cell diameter and cytosolic synthetic activity. Cell accumulation in the G2M phase, without much change in the cell cycle progression through the S phase, was observed using flow cytometry.Although the tumour cells showed a greater sensitivity to low bleomycin concentrations compared to the normal cells, both cell types exhibited equal sensitivity to higher drug concentrations.Provided that tumour cells are also preferentially affected by bleomycin in vivo, these findings raise the possibility that bleomycin cytotoxicity can be reduced or avoided in normal tissue.
Diethylbenzene‐induced sensorimotor neuropathy in rats
Authors: Gagnaire F. , Marignac B. , de Ceaurriz J. 
Published: October 2006

AbstractThe commercial isomer mixture of diethylbenzene (DEB mixture), 1,2‐diethylbenzene (1,2‐DEB), 1,3‐diethylbenzene (1,3‐DEB) and 1,4‐diethylbenzene (1,4‐DEB) were administered orally to male Sprague‐Dawley rats. The experimental rats and the appropriate controls were examined electrophysiologically for motor and sensory conduction velocities (MCV and SCV), and for the amplitude of the sensory action potential (ASAP) of the tail nerve, at weekly or bi‐weekly intervals. Oral administration of DEB mixture (750 or 500 mg kg−1, once daily, 5 days per week for 10 weeks) and 1,2‐DEB (100 mg kg−1, once daily, 4 days per week for 8 weeks) produced a time‐dependent decrease in MCV, SCV and ASAP. Rats treated with DEB mixture and 1,2‐DEB exhibited a blue discoloration of tissues and urine.No changes in MCV, SCV and ASAP developed in rats administered orally with 1,3‐DEP and 1,4‐DEB (500 mg kg−1, once daily, 5 days per week for 8 weeks).The results indicate that 1,2‐DEB is the isomer responsible for neurotoxicity and suggest that a metabolic pathway giving rise to coloured compounds is involved in the neurotoxicity of DEB.
Carcinogenic oil fractionation and nuclear enlargement in mouse skin
Authors: Ingram A. J. 
Published: October 2006

AbstractSUMMARY A non‐solvent‐refined oil, previously shown to produce tumours in a long‐term skin painting assay and a positive result in the mouse skin nuclear enlargement test, was separated using silica gel elution techniques into eight fractions. Fraction 1, which contained saturated and 1–2 ring aromatic hydrocarbons, was used to dilute the other fractions to produce solutions equivalent to and twice their original concentration in the intact oil. Fraction 1, diluted fractions 2–8, the reconstituted oil, the original oil and a negative control oil were examined for their ability to produce nuclear enlargement.The degree of nuclear enlargement observed with fraction 1 was considered to indicate marginal or no carcinogenic activity. With the fraction that contained 2–3 ring aromatic compounds, weak carcinogenic activity could not be ruled out but it is unlikely that these components played a major role in the carcinogenicity of the oil. The greatest activity was identified in the fraction containing the total 3/4–6 ring polycyclic aromatic hydrocarbons (PAHs) and further fractionation of this suggested that the parent 4–6 ring PAHs were responsible for more than half the activity of the intact oil, despite being present at only 0.06%. The fraction that contained polar compounds showed no activity. The reconstituted oil showed slightly less activity than the original oil. Other fractions, which contained alkylated PAHs, did not seem to have much activity. These findings, which are in close agreement with published evidence on tumour induction by fractions of oils and coal liquids, suggest that the components responsible for inducing nuclear enlargement are the same as those responsible for skin tumour induction. The results also suggest that estimates of carcinogenic activity made from analytical findings, such as the weight of DMSO extractable material, or even from the total 3–6 ring PAHs may be misleading as the main active components form such a small proportion of the material measured.
Alterations in xenobiotic metabolizing enzymes in brain and liver of rats coexposed to endosulfan and malathion
Authors: Srikanth Nadadur S. , Seth Prahlad K. 
Published: October 2006

AbstractThe effects of endosulfan (3 mg kg−1 body wt., i.p.) and malathion (30 mg kg−1 body wt.) and their coexposure on rat hepatic and brain xenobiotic metabolizing enzymes were investigated. Endosulfan was found to induce aminopyrine‐n‐demethylase (81%) and aniline hydroxylase (59%) activities significantly in liver and to a lesser extent in brain. Malathion treatment induced malathion carboxylesterase activity in both liver (50%) and brain (22%), significantly depleted liver glutathione (35%) content with stimulation of glutathione‐S‐transferase (50%) and inhibited the activity of mixed‐function oxidases. In the coexposed animals, malathion's inhibitory influence on mixed‐function oxidases and endosulfan's inhibitory effect on malathion carboxylesterase were found to dominate, while endosulfan potentiated the activity of glutathione‐S‐transferase significantly in liver (69%) and brain. A similar trend of alteration in coexposed brain was found, but to a lesser extent. A significant inhibition in brain acetylcholine esterase activity (42%) in the coexposed animals suggests that endosulfan may potentiate the toxicity of malathion by interfering with glutathione and carboxylesterase routes of malathion detoxification.
Identification of contact allergens using the murine local lymph node assay: Comparisons with the buehler occluded patch test in guinea pigs
Authors: Kimber I. , Hilton J. , Botham P. A. 
Published: October 2006

AbstractA murine local lymph node assay has been developed for the identification of contact sensitizing chemicals. In the present study, the performance of the local lymph node assay has been evaluated with twenty‐four coded chemicals of previously unknown skin sensitizing potential and the results compared with predictions made from concurrent occluded patch tests (Buehler tests) in guinea pigs. The data presented demonstrate that the local lymph node assay successfully identified those chemicals that were classified'as moderate or strong skin sensitizers in the Buehler test. In the present series of experiments, chemicals predicted to be mild sensitizers in the Buehler test were classified as not strong sensitizers' in the local lymph node assay. In the majority of instances, the Buehler test and local lymph node assay were in agreement with regard to the identification of non‐sensitizing chemicals. However, two chemicals that were classified as non‐sensitizers in the guinea pig test exhibited positive responses in the local lymph node assay and were predicted to be sensitizers. Some coloured chemicals resulted in obscured Buehler readings and, here, assessment was based upon histological examination of the challenge site. These compounds were examined also in the local lymph node assay and similar predictions of sensitizing potential were made.Taken together, the data reveal close, but not absolute, concordance between the local lymph node assay and the Buehler test. The relative merits of these predictive test methods are discussed.
Developmental toxicity of vanadium in mice after oral administration
Authors: Paternain J. L. , Domingo J. L. , Gómez M. , Ortega A. , Corbella J. 
Published: October 2006

AbstractVanadium, as vanadyl sulphate pentahydrate, was evaluated for its embryotoxic, fetotoxic and teratogenic potential in Swiss mice. The compound was administered by gavage to pregnant mice at doses of 0, 37.5, 75 or 150 mg kg−1 day−1 on days 6–15 of pregnancy. On gestation day 18, all live fetuses were examined for external, visceral and skeletal malformations and variations. Maternal toxicity was observed in the vanadium‐treated animals, as evidenced by reduced weight gain, reduced body weight on gestation day 18 (corrected for gravid uterine weight) and decreased absolute liver and kidney weights at 75 and 150 mg kg−1 day−1. The number of total implants, live and dead fetuses, late resorptions, the sex ratio and the post‐implantation losses were not significantly different between the vanadium‐treated mice arid the controls. However, there was a significant increase in the number of early resorptions per litter at all dose levels. Fetotoxicity was evidenced by lower fetal weights and fetal lengths, and the presence of developmental variations. Malformation incidence also was increased by the administration of vanadium. Thus, the no observable effect level' (NOEL) for maternal toxicity, embryofetotoxicity and teratogenicity for vanadyl sulphate pentahydrate under these test conditions was below 37.5 mg kg−1 day−1 for Swiss mice.