bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathology and tumor development through time in guppies dosed with diethylnitrosamine (DEN)
Authors: Parland William K. , Baumann Paul C. 
Published: October 2006

AbstractWithin the last decade unusually high frequencies of neoplasms have been reported in feral fish populations from a variety of locations. At many of these locations organic carcinogens have been noted as a potential cause. We sought to identify toxic effects including neoplasia in fish exposed to an organic carcinogen, and to quantify these effects through time.We exposed guppies (Poecilia reticulata) to multiple doses of DEN, an organic carcinogen. Fish were then subsampled and examined for liver histopathology at 2‐month intervals over 12 months. Necrotic zones, macrophage centers, bile duct proliferations, enlarged lipid deposits, neoplastic foci, cholangiocarcinomas and hepatoblastomas were quantified by frequency of occurrence and the percentage of liver area involved.DEN toxicity resulted in necrotic zones that peaked in frequency at the first sample period (2 months). Lipid deposits increased, then plateaued in guppies, indicating a more chronic toxic effect. Similarly, macrophage centers increased through the sampling period. Bile duct proliferation appeared to be of two types: a reversible toxic response which peaked at 4 months and then declined and a less frequent irreversible proliferation which continued to develop into cholangiocarcinoma. Neoplastic foci of mixed hepatocytes and cholangiocytes increased in livers of exposed guppies from the second month, developing into hepatoblastomas, which occurred in almost 100% of exposed guppies by the twelfth month. The irreversible bile duct proliferations and the neoplastic foci had cellular densities different from corresponding control tissue and similar to cellular densities of cholangiocarcinomas and hepatoblastomas, respectively.
Excretion of 3‐hydroxy‐benzo(a)pyrene and mutagenicity in rat urine after exposure to benzo(a)pyrene
Authors: Jongeneelen F. J. , Leijdekkers Ch. M. , Bos R. P. , Theuws J. L. G. , Th. Henderson P. 
Published: October 2006

Abstract3‐hydroxy‐benzo(a)pyrene (3‐OH‐B(a)P) and mutagenic activity in rat urine were determined after the oral administration of benzo(a)pyrene given in three repeated doses of 10, 20 and 50 μmol kg−1. The procedure for the determination of 3‐OH‐B(a)P consisted of enzymic hydrolysis, separation and HPLC‐analysis. The mutagenic activity of concentrated urine samples was assayed with the Salmonella typhimurium strain TA98 in the presence of S9 mix and β‐glucuronidase. The urinary excretion of 3‐OH‐B(a)P and mutagens showed a correlation and both increased dose‐dependently during the sampling period of 6 days. Data indicated that 3‐OH‐B(a)P can be regarded as a reliable representative of all urinary (pre)‐mutagens derived from benzo(a)pyrene and exposure of rats to benzo(a)pyrene could be detected with greater sensitivity by the HPLC assay of 3‐OH‐B(a)P than with the non‐specific mutagenicity assay.
Method for determining the lung burden of talc in rats and mice after inhalation exposure to talc aerosols
Authors: Hanson R. L. , Benson J. M. , Henderson T. R. , Carpenter R. L. , Pickrell J. A. , Brown S. C. 
Published: October 2006

AbstractA method has been developed to quantitate talc lung burdens in rats and mice after inhalation exposure to talc aerosols. The method is based on acid‐insoluble magnesium (Mg) determination by flame atomic absorption. Precipitating protein from homogenates of lungs of unexposed rodents with 5% perchloric acid and washing with 5% trichloroacetic acid removed the soluble and naturally occurring Mg. This resulted in residual Mg content averaging 0.43 μg Mg per g lung in rats and less than 0.1 μg Mg per g lung in mice for young rodents less than 12 weeks old. Rodents 12–18 months old had residual mean (±SD) Mg contents of 3.4 ± 2.0 μg Mg per g rat lung (n =17) and 6.5 ± 2.9 μg Mg per g mouse lung (n =12). Thus, the background residual acid‐insoluble Mg content in rodent lungs appears to increase with age. Negligible quantities of Mg were extracted directly from the talc treated by these procedures. Adding 50–2000 μg talc to lungs from unexposed rodents, followed by the sample treatment, gave mean (±SD) Mg recoveries of 89 ± 12% (n =19) for rat lungs and 96 ± 26% (n =15) for mouse lungs. The lung burden of talc in rodents exposed to talc aerosols for 6 h per day, 5 days per week for 4 weeks was determined. Mean lung burdens in rats were 77, 187, and 806 μg talc per g lung (n =10) for exposures at 2.3, 4.3, and 17 mg talc m3, respectively. Mean lung burdens in mice were 114, 325 and 1150 μg talc per g lung (n =10) for exposures at 2.2, 6.3 and 20.6 mg talc m3, respectively. The coefficient of variation for the lung burdens of the different exposure groups ranged from 8 to 21%.
Effects of formaldehyde and acetaldehyde inhalation on rat pulmonary mechanics
Authors: Nascimento Saldiva Paulo Hiláro , do Rio Caldeira Marina Pires , Massad Eduardo , Calheiros Débora Fernandes , Cardoso Luiza Maria Nunes , Miklós Böhm György , Saldiva Carmen Diva 
Published: October 2006

AbstractTwo groups of 12 male Wistar rats received either 243 ppm of acetaldehyde or 5.7 ppm of formaldehyde for 8h a day, 5 days a week during 5 weeks. These levels represent three times the threshold limit values (TLV) for these substances in Brazilian legislation. The animals were evaluated by pulmonary function tests before and after exposure to the pollutants. The data obtained from these rats were compared with those of 12 controls, housed in identical conditions for the same length of time but breathing normal air. The results showed an increase of the functional residual capacity, residual volume, total lung capacity and respiratory frequency in the rats exposed to acetaldehyde atmosphere. The animals exposed to formaldehyde did not present pulmonary function alterations when compared with the controls. The damage caused by acetaldehyde to the peripheral regions of the lung parenchyma, affecting small airways or altering pulmonary elastic properties, is discussed. It is suggested that the Brazilian TLV for acetaldehyde (78 ppm) is not as safe as that for formaldehyde (1.6 ppm).
Fractionation of diesel particle extracts by sephadex LH‐20 and thin‐layer chromatography
Authors: Bechtold W. E. , Dutcher J. S. , Brooks A. L. , Henderson T. R. 
Published: October 2006

AbstractA method was developed to concentrate fractions high in bacterial mutagenicity from diesel exhaust particle (DEP) extracts. The two‐step fractionation of organic extracts of DEP employed Sephadex LH‐20 followed by thin‐layer chromatography (TLC). In both steps, nitro‐substituted polycyclic aromatic hydrocarbons (nitro‐PAHs) were found to co‐elute with the fractions of highest specific bacterial mutagenic activity. Although recoveries of mass and mutagenicity from the LH‐20 fractionation were high, very low (20–30%) recovery of mutagenicity was found after TLC. Recovery studies using 14C‐labeled 1‐nitropyrene showed that 78% of the compound was recovered unaltered through the combined fractionation. The most bioactive TLC subfraction was chromatographed using gas chromatography with thermionic specific detection. A sizeable peak was found to co‐elute with a nitropyrene standard, but no peak was found co‐eluting with nitrofluoranthene. Triple quadrapole mass spectrometry was used to measure the concentrations of nitropyrene in each of the fractions. Nitropyrene was enriched 160‐fold in the most bioactive TLC subfraction over the starting material, for a final concentration of over 3200 μg g−1. Masses corresponding to several two‐ and three‐ring methylated nitro‐PAHs were found in the same fraction, including nitro‐(methylbiphenyls/methylacenapthenes) and nitro‐(methylanthracenes/methylphenanthrenes).
Welding fumes and chromium compounds in cell transformation assays
Authors: Hansen Karen , Stern Richard M. 
Published: October 2006

AbstractFumes generated from mild steel and stainless steel welding were collected on paper filters and tested in the BHK and SHE cell transformation assays. Fumes from the manual metal arc welding of stainless steel (MMA/SS) had a toxic and transforming effect attributable to their Cr(VI) content. The fumes from metal inert gas stainless steel (MIG/SS) welding also had a toxic effect but this was 2–3 times greater than that expected from their soluble Cr(VI) content based on the activity of soluble Cr(VI) from pure chromium compounds. When collected in an impinger, the fumes from MIG/SS were found to contain approximately 10 times the soluble Cr(VI) content of samples collected on filters. This additional Cr(VI), when collected in a water impinger, also exhibited a greater toxicity compared with that found for the additional Cr(VI) collected in an impinger filled with growth medium. This comparison implies the presence of a short‐lived biologically active Cr(VI) species usually lost in conventional sampling techniques. It also implies that there is a detoxification step associated with the formation of Cr(VI) organic complexes. Relatively insoluble Cr(VI) compounds showed a higher toxic and transforming effect in the BHK assay than could be ascribed to the soluble Cr(VI) content of the medium, indicating the importance of phagocytosis as a pathway for the uptake of Cr(VI) and other toxic substances from particulates.
Oxidant gas injury to the lung: A discussion on the functional implications
Authors: Guidotti Tee Lamont 
Published: October 2006

AbstractAcute toxic inhalation by the oxidant gases, particularly ozone (O3), nitrogen dioxide (NO2) and oxygen (O2) at high tension, has been assumed to be no more than a chemical burn of the epithelial surface. More recently, oxidant toxic inhalation has been appreciated as a complex process involving biochemical, morphological and functional changes which are qualitatively similar although inducible by different agents. Recent advances in pulmonary pathophysiology, inhalation toxicology and particularly endothelial biology now challenge the validity of a theoretical framework which seemed almost complete just 5 years ago. Considerable attention has been paid in recent years to the biochemical events occurring at the moment of and immediately following exposure to the oxidant gases. Progress in elucidating the initial events has been rapid and promises a more complete picture in the near future. Studies of the pathophysiologic mechanisms associated with toxic inhalation by the oxidant gases have been relatively static, however. In this discussion, implications of recent findings in related fields were examined in an effort to identify new hypotheses and directions for investigation.
Partition coefficients of mercury (203Hg) vapor between air and biological fluids
Authors: Hursh J. B. 
Published: October 2006

AbstractOstwald partition coefficients for mercury (Hg203) vapor (ng Hg per ml fluid/ng Hg vapor per ml air) were determined for human whole blood, 10.50 (10 °C), 6.62 (22 °C), 4.20 (37 °C); for human plasma, 5.56 (10 °C), 3.63 (22 °C), 2.40 (37 °C); for 0.9% NaCl; 2.65 (22 °C); and for sunflower oil, 80.8 (22 °C). It was shown that the uptake of mercury vapor by whole blood can not be accounted for as the sum of the solubilities of the saline and lipid components, but that when the uptake by hemoglobin is included the agreement is satisfactory. Using the solubility of mercury vapor as determined in this paper, consideration was given to various mechanisms for mobilization of mercury vapor from the lung. The method used for these determinations is recommended for similar studies because of its simplicity and precision.
Evaluation of the systemic toxicity of coal liquefaction‐derived materials following repeated dermal exposure in the rabbit
Authors: McKee Richard H. , Kapp Robert W. , Ward Dennis P. 
Published: October 2006

AbstractThe subchronic toxicity of two materials produced by the EDS direct coal liquefaction process was investigated using adult New Zealand white rabbits as the test species. Recycle solvent (RS: 204–427°C) and fuel oil (FO: 204–538°C) were applied to the intact dorsal surface of rabbits, 5 days per week for 4 weeks. Materials were applied as suspensions (2.5 and 10.0 g 100 ml−1) in white oil. White oil alone was administered to concurrent control groups. Both RS and FO elicited gross signs of toxicity including severe dermal irritation, loss of body weight (16–25%) and mortality (4/20 in the high‐dose group treated with RS). Systemic effects included liver enlargement as evidenced by histologic findings of diffuse hepatocytomegaly, cytoplasmic degeneration and hepatocellular vacuolation as well as elevated serum cholesterol. There was also evidence of testicular, seminal vesicle and thymic atrophy. More pronounced effects were apparent in the high‐dose groups. Testes and epididymides from four of the five FO‐treated male rabbits were unremarkable at the microscopic level. The testes, epididymides and seminal vesicles of the fifth animal were atrophic. Three of ten RS treated rabbits showed testicular atrophy associated with hypo‐spermatogenesis in the testes, aspermia in the epididymides and vesiculitis in the seminal vesicles. Four additional animals showed evidence of seminal vesicle atrophy. The liver enlargement was probably due to compensatory metabolism; however, exposure to similar materials at higher levels has resulted in liver toxicity. Thymic and testicular atrophy may have been a secondary response to dermal irritation, stress or body weight loss.
Effect of phorone‐induced glutathione depletion on the metabolism and hepatotoxicity of carbon tetrachloride and vinylidene chloride in rats
Authors: Siegers C.‐P. , Horn W. , Younes M. 
Published: October 2006

AbstractAlthough the depletion of hepatic glutathione in male rats following treatment with phorone (diisopropylidene acetone) did not affect the xenobiotic‐metabolizing microsomal enzyme system, the metabolic elimination of vinylidene chloride (VDC) from the atmosphere of a closed exposure system was inhibited. However, the hepatotoxicity of VDC was enhanced after GSH‐depletion, although no enhancement of VDC‐induced in vivo lipid peroxidation was observed. In contrast, GSH depletion had no influence on the metabolic elimination of carbon tetrachloride, but augmented both the hepatotoxic response to and the in vivo lipid peroxidation induced by CCl4. In the case of VDC GSH‐depletion hepatoxicity was increased because of a change in the metabolic pathway, resulting in production of intermediates of greater toxicity: lack of GSH in CCl4 treated rats renders membrane phospholipids more susceptible to peroxidative damage.
The hepatotoxicity of carbon disulphide in sheep
Authors: Wilkie I. W. , Seawright A. A. , Hrdlicka J. 
Published: October 2006

AbstractCarbon Disulphide (CS2) caused liver injury when dosed orally (intraruminally) at 0.05 ml per kg body weight to overnight fasted sheep which had been given 200 mg kg−1 DDT intraruminally 1 week previously to enhance the hepatic mixed function oxygenases. The liver lesion was a periacinar hepatocellular vacuolar degeneration, fully developed at 24h and lasting from 4 to 5 days after which the hepatic morphology returned to normal. At 24h after dosing with CS2 there was an increase in total liver water, sodium and potassium ions but without an increase in the concentration of these cations in total liver water, and a 50% reduction in microsomal cytochrome P450 levels. Calcium concentration was either unchanged or only slightly increased. The cytoplasmic vacuoles were mainly distensions of the rough endoplasmic reticulum and contained fine amorphous or fibrillary material, probably originating from damaged smooth endoplasmic reticulum membranes. The transient influx of fluid into these organelles is thought to be due to osmotic action generated by molecules derived from the latter macromolecular membrane fragments. The lesion resembles that seen in the rat due to CS2 after pretreatment with phenobarbitone. In situations in which sheep are drenched with CS2 and CCl4 in combination, it is suggested that the development of hepatic periacinar hydropic change due to the CS2 in animals normally susceptible to CCl4 because of enhanced microsomal cytochrome P450 levels would provide a better chance of survival than if CCl4 alone was administered and extensive periacinar coagulative necrosis occurred.
The mechanisms of action of cyanide on the rabbit aorta
Authors: Robinson Casey P. , Baskin Steven I. , Franz David R. 
Published: October 2006

AbstractPretreatment of strips of rabbit aorta with 10−3 M sodium cyanide reduced contractions to 10−8 through 10−4 M norepinephrine (NE) added cumulatively. This antagonism by cyanide was not altered by 4 × 10−6 M ouabain or verapamil, suggesting a lack of involvement of Na+, K+ ATPase or of calcium influx in the antagonism. Cyanide potentiated contractions caused by 3 × 10−3 M potassium, but reduced contractions induced by higher potassium concentrations. Because the antagonism of higher concentrations of potassium and NE were similar, it seems that selective actions on different calcium pools are possibly not involved in the antagonism of agonist‐induced contractions. 10−2 M cyanide contracted rabbit aorta with a mean contraction 16% of that induced by 10−4 M NE. These contractions were potentiated by pretreatment with 4 × 10−6 M ouabain and 4 × 10−6 m verapamil but were unaffected by the serotonin antagonist 2‐bromo lysergic acid diethylamide, 10−4 M (2‐BrLSD), the alpha adrenergic antagonist phentolamine, 4 × 10−5 M, the H1 antihistaminic pyrilamine, 10−5 M, or the antimuscarinic atropine, 10−6 M. The contractions were reduced by 10−4 M 4,4′‐di‐isothiocyano‐2,2′‐stilbene disulfonic acid (DIDS) or chlorpromazine. The reduction may be due to a blockade of anionic channel mechanisms facilitating entry of cyanide into the vascular smooth muscle cell, as both of these agents can block anionic channels in other tissues.
Embryotoxicity of benzalkonium chloride in vaginally treated rats
Authors: Buttar Harpal S. 
Published: October 2006

AbstractThe effects of the spermicide benzalkonium chloride (BKC) were studied on the conceptus of rat. Single doses (0, 25, 50, 100 or 200 mg kg−1) of aqueous solutions of BKC were administered intravaginally (1 ml kg−1) on gestational day 1. The vulval metallic clips, used to prevent leakage of the solution, were removed 24 h post‐treatment. Fetuses were obtained and examined for malformations on day 21 of gestation. Slight to copious amounts of vaginal discharge and vaginitis were noticed in rats treated with the two largest doses of BKC. A dose‐related increase in resorptions and fetal death, reduction in litter size and weight were observed in BKC‐treated dams. The conceptus loss seemed to occur both before and after implantation. BKC did not cause any discernible visceral malformations, although minor sternal defects occured in fetuses exposed to 100 and 200 mg kg−1 of the spermicide. These results suggest that single vaginal application of BKC is embryo‐ and fetocidal in the rat at a dose about 143 times higher than that recommended for controlling conception in women.
Toxicity of aromatic disulphides. I. Generation of superoxide radical and hydrogen peroxide by aromatic disulphides in vitro
Authors: Munday R. 
Published: October 2006

AbstractThe aromatic thiol, thiophenol, is readily autoxidized at neutral pH in a reaction which generates superoxide radical and hydrogen peroxide. The oxidation product, diphenyl disulphide, may be reduced back to thiophenol by glutathione and in the presence of an excess of the latter thiol a reduction/autoxidation cycle for generation of ‘active oxygen’ species is established. The autoxidation reaction is strongly catalyzed by haematin; hemoglobin is also an effective mediator of ‘active oxygen’ generation from the diphenyl disulphide/glutathione couple, being oxidized to methemoglobin in the process.Certain derivatives of diphenyl disulphide also generate superoxide radical and hydrogen peroxide in the presence of glutathione, although the rate of the reaction is strongly influenced by the nature of the substituent groups. Among the ring‐substituted derivatives of diphenyl disulphide investigated, the rate of ‘active oxygen’ production decreased in the order 4‐amino > 2‐amino > 4‐methyl > unsubstituted > 4‐nitro > 2‐carboxyl; little reaction was detected with the homologous compound, dibenzyl disulphide.
Toxicity of aromatic disulphides. II. Intra‐erythrocytic hydrogen peroxide formation and oxidative damage by aromatic disulphides
Authors: Munday R. 
Published: October 2006

AbstractDiphenyl disulphide has been shown to generate hydrogen peroxide in erythrocytes in vitro. It also induces oxidative damage (reversible and irreversible haemoglobin oxidation, depletion of non‐protein and protein‐bound thiols) in these cells.Such changes were also recorded in erythrocytes exposed to 4,4′ ‐diaminodiphenyl disulphide, 2,2′‐diaminodiphenyl disulphide, 4,4′‐dimethyldiphenyl disulphide, 4,4′‐dinitrodiphenyl disulphide, diphenyl disulphide‐2,2′‐dicarboxylic acid and dibenzyl disulphide. The relative potency of these coumpounds in causing erythrocyte damage is correlated with their ability to generate ‘active oxygen’ species in vitro.
Short‐term toxicity studies of vanadium in rats
Authors: Domingo J. L. , Llobet J. M. , Tomas J. M. , Corbella J. 
Published: October 2006

AbstractVanadium (in the form of NaVO3) was given in drinking water to groups of 10 male Sprague‐Dawley rats over a period of 3 months at concentrations of 0, 5, 10 and 50 ppm. Vanadium accumulated dose‐dependently in the kidneys and spleen. Appearance, behaviour, food and water consumption, growth and mortality of the treated rats of all groups were not affected during the 3‐month period. Histopathological investigation showed only mild though dose‐dependent lesions in kidneys and spleen. The plasma concentrations of urea and uric acid were increased in the highest exposure groups.
Uptake of cadmium in isolated kidney cells—influence of binding form and in vivo pretreatment
Authors: Jin Taiyi , Nordberg Gunnar F. , Nordberg Monica 
Published: October 2006

AbstractUptake of cadmium as 109CdCl2, 109Cd‐cysteine, 109Cd‐albumin and 109Cd‐metallothionein was studied in isolated kidney cells from rat. Cd as 109CdCl2 and 109Cd‐albumin was taken up at similar rates. The uptake of cadmium as 109Cd‐cysteine was greater and that of 109Cd‐metallothionein lower compared with that of the other substances. These observations were made on non‐pretreated cells. In cells taken from rats pretreated with CdCl2 in vivo, the uptake of cadmium as 109CdCl2, 109Cd‐cysteine and 109Cd‐albumin was lower than in cells from non‐pretreated rats. However, the uptake of 109Cd‐metallothionein was considerably enhanced in pretreated cells. In pretreated kidney cells the decreased uptake of Cd (as Cd‐albumin) might be related to protection of the kidney against acute Cd toxicity and increased uptake of metallothionein‐Cd might contribute to the explanation of renal damage in long‐term Cd exposure.