bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carcinogenic evaluation of 2,3‐dimethyl‐2,3‐dinitrobutane via the mouse skin bioassay
Authors: Reddy Tirumuru V. , Daniel F. Bernard , Robinson Merrel , Olson Greg R. 
Published: October 2006

AbstractFemale SENCAR mice initiated with 2,3‐dimethyl‐2,3‐dinitrobutane (DMDNB) and promoted with 12‐Otetradecanoylphorol‐13‐acetate (TPA) via the SENCAR mouse skin bioassay did not exhibit a significant increase in skin tumors. The mice received 20 mg kg−1 DMDNB divided into six intragastric doses over 2 weeks and were promoted three times per week for 20 weeks.
28‐day inhalation study of a cross‐linked polyacrylate superabsorbent in the Hamster
Authors: McGrath James J. , Purkiss Laquetta , Eberle Mary , McGrath W. R. 
Published: October 2006

AbstractMale and female Syrian Golden hamsters (20 of each sex) breathed respirable cross‐linked polyacrylate dust (0.3, 1.0 or 10 mg m−3) for 6 h a day, 5 days a week for 28 exposures. More than 99% of the particles were 3–4 μm or smaller. No differences in overall health or body weight were observed among the groups, nor were there deaths during exposure or during the post‐exposure period.In animals killed within 24 h after the final exposure, foreign material was detected in the lungs in a doserelated manner. In animals examined 4 weeks post‐exposure, much of this material had been cleared from the lungs. There was a significant alveolar macrophage and a non‐significant inflammatory cell response following exposure; both responses appeared to decrease during the post‐exposure period. There was no evidence of fibrosis in the low‐ or medium‐exposure groups after the exposure or post‐exposure periods. In the high‐exposure group there was equivocal evidence of fibrosis in one set of lungs at the end of the exposure and in another set after the post‐exposure period.These results indicate that subacute exposure of Syrian Golden hamsters to low concentrations of cross‐linked polyacrylate dust in particle sizes capable of reaching deep lung structures does not cause pulmonary fibrosis in the hamsters and that resolution of the cellular response induced by these particles occurs. These results also indicate that the test material was cleared from the lung following termination of exposure.
The local lymph node assay: An interlaboratory evaluation of Interleukin 6 (IL‐6) production by draining lymph node cells
Authors: Dearman R. J. , Ramdin L. S. P. , Kimber I. , Scholes E. W. , Basketter D. A. 
Published: October 2006

AbstractThe murine local lymph node assay is a predictive method for the identification of skin‐sensitizing chemicals in which activity is measured as a function of proliferative activity induced in lymph nodes draining the site of exposure. In the present study, the induction by topically applied chemicals of draining lymph node cell (LNC) production of the cytokine interleukin 6 (IL‐6) has been evaluated as an alternative endpoint for the local lymph node assay. In addition, results derived from studies of IL‐6 production by LNC performed independently in two separate collaborating laboratories have been compared. Of the nine skin sensitizing chemicals examined, six provoked detectable levels (>150 pg ml−1) of IL‐6 production by draining LNCs (as measured by enzyme‐linked immunosorbent assay) following exposure of mice to at least one test concentration of the material in both of the laboratories. Three other sensitizing chemicals failed to induce measurable IL‐6 production at any test concentration in either one or both of the participating laboratories. Both of the non‐sensitizing chemicals evaluated (sodium lauryl sulphate and methyl salicylate) also failed to result in detectable IL‐6 synthesis. There was a high level of agreement between the two laboratories. The rank order of chemicals with respect to IL‐6 production by LNCs was identical in both cases, as was the dose‐response relationship observed with each test material.These data reveal that, although inducible IL‐6 production by draining LNCs provides a robust approach to the measurement of strong sensitizing activity, as performed here the method is of insufficient sensitivity for the routine identification of skin allergens.
Woodworkers' exposure to tannins
Authors: Bianco M.‐A. , Savolainen H. 
Published: October 2006

AbstractThe tannin concentration of hard‐ and soft‐wood dust was determined in dust powder and in samples on filters. It varied from 1.6 ± 0.3 mg g−1(± SD) for fir, which is a soft wood, to 80 ± 30 mg g−1(± SD) for oak, which is a hard wood. The low detection limit of the spectrophotometric method (1.5 μg per sample) made the analysis possible with no interference from cellulose ester filters. In five woodworking shops the concentrations of the total dust varied from 0.2 to 20 mg m−3, while those of tannins varied from 2 to 341 μg m−3. As hard woods like oak or mahogany have a higher tannin concentration than soft woods, tannin concentration analysis in wood dust can be used as an indicator of exposure to hard‐wood dust.
Early hepatic changes induced by nuarimol in rats
Authors: Kostka Grazyna , Palut Danuta , Kopeć‐Szlȩzak Joanna 
Published: October 2006

AbstractIt is commonly believed that in short‐term tests hepatic cytochrome P‐450b inducers stimulate liver enlargement and mitogenesis in the absence of overt hepatotoxic effects. In this investigation male Wistar rats received naurimol (an organochlorine pesticide) in one, three and five oral doses of 31.5, 62.5 and 125 mg kg−body wt. day−, whereupon the effects on liver were determined. The early effects were dose‐dependent increases in p‐nitroanisole metabolism, hepatocyte proliferation (DNA synthesis and mitotic activity) and liver weight. Five administrations of the lowest does (31.5 mg kg−1body wt. day−1) did not change liver weight, despite increased p‐nitroanisole metabolism and hepatocyte proliferation. In contrast to p‐nitroanisole metabolism and hepatomegaly, proliferation was only transient and disappeared even when treatment continued. The increase in binuclear hepatocytes and signs of necrosis suggested that the hepatomitogenic effect of nuarimol reflected a regenerative response, which may simulate the proliferation caused by partial hepatectomy.
Effects of lead loads on branchial osmoregulatory mechanisms in the rainbow trout Oncorhynchus mykiss
Authors: Sola François , Masoni Armand , Isaia Jacques 
Published: October 2006

AbstractExposure of rainbow trout to lead chloride (PbCl2, 1 ppm) in fresh water killed all animals within 16 days. Exposure to this lethal dose for 6 days only showed a significant increase in the haematocrit. Calcium, sodium and chloride concentrations in plasma were not notably modified. Both the influx and the net flux of sodium fluctuated much less than the diffusional water fluxes through secondary lamellae in gills. Branchial Na,K‐ATPase, Ca‐ATPase and HCO3‐ATPase activities were not sensitive to lead toxicity. Lead caused a cellular ‘wave‐shaped’ degeneration and renewal with modification in the number and morphology of chloride cells. Results are discussed in relation to the hydromineral balance of the trout.
Effect of protein malnutrition on the neurobehavioural toxicity of styrene in young rats
Authors: Khanna Vinay K. , Husain Raushan , Seth Prahlad K. 
Published: October 2006

AbstractNeurotoxic effects of styrene on certain biochemical and behavioural indices were studied in young rats kept deficient in protein during the weaning period. Young rats fed a low‐protein diet showed a significant decrease in the level of dopamine and an increase in frontocortical [3H]serotonin binding in comparison to the group of rats fed a normal protein diet. These rats also showed a significant increase in foot shock‐induced aggressive behaviour, while no changes in amphetamine‐induced locomotor activity, levels of norepinephrine and serotonin and binding of [3H]spiperone to striatal membrane were observed. On exposure to styrene, rats fed a normal protein diet showed a decrease in dopamine level and an increase in foot shock‐induced aggressive behaviour only, with no significant change in other parameters, in comparison to the respective controls. It was, however, interesting to note that when rats fed a low‐protein diet were exposed to styrene they showed a significant decrease in the levels of norepinephrine, dopamine and serotonin and an increase in the binding of [3H]spiperone and [3H]5‐HT to striatal and frontocortical membranes, respectively. A significant increase in foot shock‐induced aggressive behaviour and amphetamine‐induced locomotor activity was also observed in this group of animals in comparison to those fed a low‐protein diet. The biochemical and behavioural data indicate that protein deficiency makes young animals more vulnerable and it is an important predisposing factor in the neurobehavioural toxicity of styrene.
Nickel hydroxy carbonate increases tumour necrosis factor alpha and interleukin 6 secretion by alveolar macrophages
Authors: Arsalane Karim , Gosset Philippe , Hildebrand Harmut F. , Voisin Cyr , Tonnel André‐Bernard , Wallaert Benoit 
Published: October 2006

AbstractThe aim of the current study was to assess the in vitro effects of nickel hydroxy carbonate (NiHC) at noncytotoxic concentrations on the production of cytokines such as tumour necrosis factor alpha (TNF‐α) and interleukin 6 (IL‐6) in alveolar macrophages (AMs). The effect of NiHC was evaluated in both unstimulated AMs and cells activated by lipopolysaccharide (LPS). Cytotoxicity was related to lactate dehydrogenase release and ATP cell content. The results confirm that NiHC at concentrations of 0.125, 1.25 and 3.125 μg NiHC 10−6 cells was not cytotoxic. The NiHC exposure of unstimulated AMs significantly increased the release of TNF‐α at all concentrations and that of IL‐6 at 1.25 μg NiHC 10−6 cells. LPS addition significantly increased the secretion of both cytokines. However, NiHC did not cause a significant increase in the release of TNF‐α and IL‐6 in LPS‐stimulated cells. In conclusion, the ability of NiHC to activate AMs and to release increased amounts of pro‐inflammatory mediators may be responsible, at least partly, for inflammation and pneumotoxicity associated with nickel exposure.
Two‐generation reproduction study on commercial hexane solvent
Authors: Daughtrey Wayne C. , Neeper‐Bradley Teresa , Duffy Jeffrey , Haddock Linda , Keenan Thomas , Kirwin Carroll , Soiefer Andrew 
Published: October 2006

AbstractThe reproductive effects of inhalation exposure to commercial hexane vapors were evaluated in Sprague‐Dawley rats. Males and females were exposed to commercial hexane vapor at target concentrations of 0, 900, 3000 or 9000 ppm for 6 h a day, 5 or 7 days a week, over two generations. In addition to pre‐breed exposures of 10 weeks' duration, exposures continued through mating, gestation and lactation. At both the F0 breed to produce F1 litters and the F1 breed to produce F2 litters, reproductive parameters were unaffected by commercial hexane exposure. The mating, fertility and gestational indices, as well as litter size and postnatal survival, were not significantly different between exposure groups. However, reductions in body weight and body weight gain were observed in both F1 and F2 litters exposed to 9000 ppm. Effects on body weight were not observed in offspring exposed to the two lower concentrations of commercial hexane. Histopathological examination of selected tissues revealed hyaline droplet nephropathy in adult F0 and F1 males exposed to 9000 ppm. This finding was anticipated and is not believed to be relevant for the assessment of human health effects. No other treatment‐related histopathological lesions were observed. Thus, exposure of rats to commercial hexane for two generations resulted in reduced body weight gains at 9000 ppm but no adverse effects on reproduction. These findings suggest that occupational exposure to commercial hexane vapors at currently recommended threshold limit value concentrations (i.e. TLV for n‐hexane is 50 ppm and TLV for other hexane isomers is 500 ppm) should not pose a reproductive hazard.
Retention of inhaled hexafluorocyclobutene in the rat
Authors: Maidment M. P. , Rice P. , Upshall D. G. 
Published: October 2006

AbstractHexafluorocyclobutene (HFCB), a cyclic analogue of perfluoroisobutene (PFIB), is a reactive gas that induces a fulminating pulmonary oedema in rats from which animals may die after an apparently asymptomatic period between 24 and 30 h, depending on the dose. To determine the dose of inhaled gas to the respiratory tract, the retention of HFCB has been determined in the rat at three inhaled concentrations with simultaneous measurement of respiratory parameters.Rats exposed continuously to HFCB retained 25%, 19% and 16% of the inhaled dose after exposure to 1.2, 6 and 30 ppm, respectively, which fell to 24%, 17% and 9% at 30 min and 21%, 16% and 6.5% after 1 h. The rate of uptake of HFCB decreased markedly at the highest concentration from 200 to 112 nmol min−1 kg−1 after 30 min and to 90 nmol min−1 kg−1 after a further 30 min. Ventilatory parameters were unchanged throughout the experiment and there was no evidence of pathological or histopathological damage at the end of the exposure.On renewal of exposure to gas after a 15‐min pause, the percentage of gas retained was unchanged from that determined previously.The results indicate that there is a saturable component within the respiratory tract that is both time and concentration dependent. Hexafluorocyclobutene does not produce direct pathological damage outside the lung, which indicates that it may react rapidly with tissue components within the lung.
Comparison of the sensory irritation response in mice to chlorine and nitrogen trichloride
Authors: Gagnaire F. , Azim S. , Bonnet P. , Hecht G. , Hery M. 
Published: October 2006

AbstractThe expiratory bradypnoea indicative of upper airway irritation in mice was evaluated during a 60‐min oronasal exposure to increasing concentrations of chlorine and nitrogen trichloride. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each chemical. Chlorine and nitrogen trichloride showed dissimilar concentration‐response curves. While the maximal response of nitrogen trichloride was reached in 10 min, the maximal response of chlorine was reached between 45 and 60 min of exposure. The results showed both chemicals to have an irritant potency of the same order of magnitude. The RD50 values of chlorine and nitrogen trichloride were 3.5 and 2.5 ppm, respectively. On the basis of a TLV‐STEL (threshold limit value for short‐term exposure limit) equal to 0.1 RD50 and a TLV‐TWA (time‐weighted average) equal to 0.03 RD50, the current TLVs for chlorine seem too high (1 and 0.5 ppm, respectively) and should be reduced to 0.5 and 0.1 ppm, respectively. For nitrogen trichloride, 0.3 ppm and 0.1 ppm are proposed as TLV‐STEL and TLV‐TWA, respectively.
Toxicological evaluation of 1‐chloroacetophenone and dibenz[b,f]‐1,4‐oxazepine after repeated inhalation exposure in mice
Authors: Kumar Pravin , Flora S. J. S. , Pant S. C. , Sachan A. S. , Saxena S. P. , Gupta S. Das 
Published: October 2006

AbstractToxicological evaluation was made on the effects of two peripheral sensory irritants (tear gases): 1‐chloroacetophenone (CN) and dibenz[b,f]‐1,4‐oxazepine (CR). Animals had a 15‐min daily inhalation exposure to average vapour concentrations of 87.6 mg CN m−3 or 1008 mg CR m−3 (both equal to 0.05 LC50) for 5 or 10 days and were sacrificed 24 h after the last exposure, when biochemical and histopathological observations were made. Both chemicals caused a significant decrease in body weight gain. Histological changes in lung, liver and kidneys were more severe after 10 than after 5 days of exposure and were more severe in CN‐exposed than in CR‐exposed mice. Organ weight to body weight ratios remained normal except for the spleen to body weight ratio, which decreased in CN‐exposed mice after both 5 and 10 days of exposure. Biochemical indicators showed a toxic response only in CN‐exposed mice, but the only consistent change was an increase in blood glucose. Hepatic alkaline phosphatase was not influenced, malondialdehyde concentration and acid phosphatase activity were increased only after 5 days of exposure and liver GSH concentration decreased after 10 days of exposure. Results indicate that CN is not only more toxic than CR in absolute terms but is also more toxic at the 5% level of their LC50.
Effect of chemical form, route of administration and vehicle on 3,5‐dichloroaniline‐induced nephrotoxicity in the fischer 344 rat
Authors: Lo Herng‐Hsiang , Valentovic Monica A. , Rankin Gary O. , Brown Patrick I. 
Published: October 2006

AbstractChloroanilines are widely used chemical intermediates for the manufacture of dyes, agricultural chemicals and industrial compounds. Nephrotoxicity occurs as one toxicity following intraperitoneal (i.p.) administration of chloroaniline hydrochlorides to rats. The purpose of this study was to examine the effect of chemical form, route of administration and vehicle on 3,5‐dichloroaniline‐induced nephrotoxicity. In one set of studies, male Fischer 344 rats (four to eight per group) were administered a single i.p. injection of 3,5‐dichloroaniline free base or hydrochloride salt, cysteine hydrochloride or ornithine hydrochloride (0.8, 1.0 or 1.5 mmol kg−1) or an appropriate vehicle and renal function monitored for 48 h. Only 3,5‐dichloroaniline hydrochloride induced nephrotoxicity that was characterized as acute renal failure. When 3,5‐dichloroaniline free base (0.8 mmol kg−1) was administered in dimethyl sulfoxide (DMSO), all rats died within 24 h. In a second experiment, the free base or hydrochloride form of 3,5‐dichloroaniline (1.5 mmol kg−1) or vehicle (0.9% saline or sesame oil, respectively) were administered orally and renal function monitored for 48 h. No evidence of nephrotoxicity was observed following either treatment. However, when the hydrochloride salt was given in 25% DMSO in 0.9% saline, all rats died within 24 h, with two rats demonstrating increased proteinuria, glucosuria and hematuria within the first 6 h after treatment. These results demonstrate that 3,5‐dichloraniline nephrotoxicity is potentiated by the administration of systemic acid, but that acid alone has no effect on renal function at the dose tested. Also, 3,5‐dichloroaniline (hydrochloride or free base form) is less toxic orally than when administered i.p. In addition, when DMSO is used as part of the vehicle, 3,5‐dichloroaniline toxicity is potentiated. Thus, chemical form, route of administration and vehicle are all important factors in 3,5‐dichloroaniline‐induced toxicity.
Role of lipid peroxidation in biliary obstruction in the rat
Authors: Muriel Pablo , Suarez Oscar R. 
Published: October 2006

AbstractThere is poor evidence about the participation of lipoperoxidative processes in liver damage induced by biliary obstruction, thus the aim of this work was to study the role of lipid peroxidation in this model of liver injury. Biliary obstruction was induced in male Wistar rats by ligation of the common bile duct; control animals were sham operated. Rats were sacrificed at different times after surgery. Liver sections were used for glycogen and lipoperoxidation quantification. Markers of liver damage were determined in serum. All serum markers of liver damage increased after 1 day of biliary obstruction. Liver glycogen content decreased 1 day after surgery. On the other hand, lipoperoxidation increased later than markers of liver damage, suggesting that it is a consequence rather than the cause of liver injury. Moreover, administration of colchiceine (a good free‐radical scavenger) or vitamin E prevented lipoperoxidation but not liver damage, confirming that lipoperoxidation does not play an important role in liver damage induced by biliary obstruction. This model of liver injury seems to be useful for testing hepatoprotective drugs that do not act as free‐radical scavengers.
Toxicological evaluation of μ‐agonists part I: Assessment of toxicity following 30 days of repeated oral dosing of male and female rats with levo‐alpha‐acetylmethadol HCl (LAAM)
Authors: Borzelleca Joseph F. , Egle John L. , Harris Louis S. , Johnson David N. , Terrill James B. , Belleville Jo Ann Nuite 
Published: October 2006

AbstractThis study evaluated levo‐alpha‐acetylmethadol hydrochloride (LAAM), a long‐acting morphine‐like (μ) agonist approved in 1993 to treat opiate dependence. Sprague‐Dawley rate (20/sex/group) were gavaged with doses of 3.0–33.5 mg kg−1 for 30 days followed by a 14‐day drug‐free recovery period. Treatment‐related effects included dose‐dependent CNS depression, decreased food consumption and body weight gain, reddish urine and abdominal staining. Tolerance developed by day 7. Mortality was dose‐dependent; deaths occurred predominantly during the first week. Increased alanine aminotransferase (SGOT, AST) and lactate dehydrogenase (LDH), observed only in high‐dose males, were associated with findings in liver. Decreases in spleen/brain weight and increases in brain/body weight ratios were seen in both sexes. Decreases in weights of heart, liver and kidney achieved statistical significance only for high‐dose groups. Kidneys of mid‐ and high‐dose groups displayed intertubular mineral/crystal deposition, focal corticomedullary mineralization and focal regenerative tubular epithelium. Centrilobular hypertrophy was observed in livers of high‐dose males and mid‐ and high‐dose females. Following the recovery period, decreased body weights and increased brain/body weight ratios occurred in mid‐dose males and low‐dose females. Weights of liver and kidney and organ/brain weight ratios were decreased in mid‐dose males. Histopathological findings observed in kidneys and livers had abated.In summary, acute and repeated administration of LAAM produced a spectrum of activity consistent with its profile as a long‐acting pure μ‐agonist which stimulates microsomal enzymes in rodents. Renal and hepatic effects seen in initially drug‐naive rats treated with morphine‐type agonists are not observed in tolerant individuals stabilized on μ‐agonists to treat opiate dependence.
Determination of free malonaldehyde formed in liver microsomes upon CCl4 oxidation
Authors: Ichinose T. , Miller M. G. , Shibamoto T. 
Published: October 2006

AbstractFree malonaldehyde formed in the microsomes prepared from livers of monkey, rat, rabbit, mouse, cow, pig, dog, sheep and horse upon CCl4 oxidation was derivatized by reaction with N‐methylhydrazine to form 1‐methylpyrazole which was subsequently analyzed by capillary gas chromatography. Among the livers from animals tested, the monkey and rat livers produced the most malonaldehyde upon CCl4 treatment. Horse liver showed the greatest resistance to CCl4 oxidation. The gas chromatography method used in the present study exhibited an accurate and specific measurement of free malonaldehyde that might provide an understanding of the biochemical process of in vitro lipid peroxidation.