bluuebunny/crossref_metadata_2025_split huggingface dataset:
The early changes in mouse skin following topical application of a range of middle distillate oil products
Authors: Ingram A. J. , King D. J. , Grasso P. , Sharratt M. 
Published: October 2006

AbstractA white spirit/naphtha, three kerosines, two gas oils and a catalytically cracked light cycle oil (LCO) were applied topically to mice, three times a week for up to 6 weeks, and skin changes were examined histopathologically at intervals.The changes within 1 week of treatment appeared to depend on the effect that the physicochemical properties of each type of product had on their penetration through the skin surface or via hair follicles. With white spirit the most prominent change was widespread epidermal necrosis occurring after the second treatment, implying that the lowest boiling point materials penetrate mainly through the surface epidermis. The earliest effects with kerosines were within and around hair follicles with epidermal degeneration developing later, suggesting a predominance of follicular entry. Gas oils and LCO produced similar changes to kerosines within 1 week, gas oils producing a slower and less severe response and LCO a more severe response. In skin examined after 1–6 weeks of treatment with all middle distillates, repeated cycles of necrosis and healing responses were evident; this implied that once the epidermal barrier layer had been damaged, follicular entry became less important.The severity of the skin changes observed with these middle distillates was probably sufficient for skin tumours to arise by a non‐genotoxic mechanism if a similar treatment regime was used in a long‐term skin painting study. A method of avoiding excessive skin irritation is therefore essential in such a study in order to obtain a reliable prediction of the human hazard of such materials.
Studies on the renal transport of trimethylpentanoic acid metabolites of 2,2,4‐trimethylpentane in rat renal cortical slices
Authors: Lock Edward A. , Strasser Josef , Bus James S. , Charbonneau Michel 
Published: October 2006

Abstract2,2,4‐Trimethylpentane (TMP), a nephrotoxic component of unleaded gasoline in male but not female rats, undergoes oxidative metabolism to yield 2,2,4‐ and 2,4,4‐trimethylpentanol, pentanoic acid and 5‐hydroxypentanoic acid. We have examined the effect of three of these pentanoic acid metabolites on the renal transport of the organic anion p‐aminohippurate (PAH) and the organic cation tetraethylammonium (TEA) in renal cortical slices from male Fischer 344 rats. 2,4,4‐Trimethylpentanoic acid, the major urinary metabolite in rats, produced a selective decrease in the accumulation of PAH without affecting TEA accumulation. Kinetic analysis showed that 2,4,4‐trimethylpenanoic acid was a competitive inhibitor of the organic anion transport system, with a Ki of 4 mM. 2,4,4‐Trimethyl‐5‐hydroxypentanoic acid also showed selective inhibition of PAH transport, while 2,2,4‐trimethylpentanoic acid was less selective and reduced both PAH and TEA transport. Additional studies with radiolabeled 2,4,4‐trimethylpentanoic acid showed that there was a time‐and concentration‐dependent accumulation of radioactivity into slices of renal cortex. However, experiments conducted at 4°C and studies with metabolic inhibitors, or with an inhibitor of organic anion transport, indicated that little of the accumulated material was entering the cell. We conclude from these studies that the pentanoic acid metabolites formed from 2,2,4‐trimethylpentane are not actively transported by the renal organic anion transport system. In summary, in vitro the pentanoic acid metabolites appear to bind to renal cortical tissue and thereby reduce the transport of PAH.
Leakage of mitochondrial and cytosolic GOT in isolated rat hepatocytes exposed to halothane: An immunohistochemical study
Authors: Kinugawa Hiroshi , Kawahara Michio , Amakata Yoshikuni , Maeda Toshihiro 
Published: October 2006

AbstractThe leakage of mitochondrial (m‐) and cytosolic (s‐) aspartate aminotransferases (glutamic‐oxaloacetic transaminase: GOT) from isolated hepatocytes exposed to halothane was investigated immunohistochemically. In control isolated hepatocytes, a large number of cells were immunopositive (m‐GOT, 85%; s‐GOT, 98.5%) at various intensities. Reaction products of m‐GOT‐immunohistochemistry (m‐GOT‐I) were seen exclusively in mitochondria, while those of s‐GOT (s‐GOT‐I) were seen in the cytoplasm. When treated with low concentrations of halothane (up to 0.75%), the number of strongly m‐GOT‐I‐immunopositive cells was reduced to half, while that of s‐GOT‐I showed no noticeable change. The number of m‐GOT‐I‐immunonegative cells showed a negligible increase, while that of s‐GOT‐I increased gradually. At higher concentrations of halothane (1% or more), strongly immunopositive cells in both m‐ and s‐GOT‐I almost disappeared, while immunonegative cell numbers predominantly increased. This study showed that the isolated hepatocyte system was not homogeneous with regard to the quantity of GOT isozymes, and that halothane could induce the leakage of these isozymes from hepatocytes, along with inducing ultrastructural abnormalities, even at the lowest concentration used (0.5%). Furthermore, the data appear to indicate that the sensitivity of isolated hepatocytes to halothane is dependent on the nature of the hepatocyte itself and on the nature of both types of GOT isozymes.
Inhibitory effect of gomisi on reductive metabolism of halothane
Authors: Jiaxiang Ni , Fujii Kohyu , Sato Nobuyoshi , Yuge Osafumi 
Published: October 2006

AbstractThe effect of Gomisi (dried ripe fruit of schizandra chinensis) on chlorodifluoroethylene (CDE) and chlorotrifluoroethane (CTE) formation was investigated. The incubation mixtures for the measurement of reductive metabolites of halothane consisted of liver microsomal suspensions, 3 mM NADPH, extract solution of Gomisi and halothane in 0.1 M potassium phosphate buffer (pH 7.4). The production of CDE and CTE was inhibited by Gomisi in a dose‐dependent way. The production were reduced to half in the presence of 0.5% Gomisi extract in the reaction mixture. The results suggest that Gomisi can inhibit the reductive metabolism of halothane in vitro; thus it may protect against halothane‐induced hepatitis.
Modulation of hepatic glutathione system of enzymes in suckling mouse pups exposed translactationally to malathion
Authors: Chhabra Saranjit K. , Hashim Shehla , Rao A. R. 
Published: October 2006

AbstractThe present study examines the transmammary modulation of the glutathione system of enzymes in the F1 generation of mouse pups postnatally exposed to malathion. Lactating Swiss albino mice received either 30 or 100 mg malathion kg−1 body wt. (98% pure) for 14 or 21 days postpartum. The acid‐soluble sulphydryl content was significantly increased (P<0.001) in the liver of 14‐day‐old pups of dams that had received the higher malathion dose. A similar significant increase was seen in the 21‐day‐old male pups of dams that had received 30 mg (P<0.05) or 100 mg (P<0.01) malathion kg−1 body wt. Dams showed an enhanced hepatic glutathione S‐transferase activity following treatment with 100 mg melathion kg−1 body wt. for 14 days (P<0.02) and 21 days (P<0.001). Pups of either age groups also showed enhanced hepatic glutathion S‐transferase activity (P<0.001). A significant enhancement in glutathione reductase activity was observed with malathion treatment in livers of dams and pups (P<0.001). However, dams that had received 30 mg malathion kg−1 body wt. daily for 21 days or 100 mg malathion kg−1 body wt. for either 14 or 21 days showed significantly reduced hepatic glutathione peroxidase activity (P<0.01, P<0.001). A significant decrease in glutathione peroxidase activity was also observed in the liver of the 21‐day‐old male (P<0.01) and female (P<0.02) pups of dams that were treated with the higher dose of malathion.
Differential sensitivity of DBA/2 and C57BL/6 mice to cyclophosphamide
Authors: Anton Elsa 
Published: October 2006

AbstractEarly and delayed toxicity of a single dose of 300 mg kg−1 cyclophosphamide (CP) was investigated in male DBA/2 and C57BL/6 mice.Early toxicity (up to 30 days after CP administration) resulted in 36.6% lethality in DBA/2 and no mortality in C57BL/6 mice. Delayed toxicity (after 30 days) occurred primarily in DBA/2 mice, resulting in a survival of 3% in DBA/2 and 93% in C57BL/6 mice on day 125 after CP administration.Early modifications brought about by CP in erythrocytes and leucocytes, and spleen and liver indexes (mg organ g−1 body wt.) were rather similar in DBA/2 and C57BL/6 strains. However, CP treatment caused a profound cell depletion in DBA/2 bone marrow owing, in part, to the fact that the number of cells in bone marrow of normal DBA/2 mice was much lower than that in normal C57BL/6 mice. Furthermore, the thymus index (mg organ g−1 body wt.) decreased sooner in DBA/2 than in C57BL/6 animals and no sign of recovery was evident in the former even after 10 days, whereas recovery in the latter started on day 5 after injection.Differential sensitivity of DBA/2 and C57BL/6 strains to CP could be due to differences in activation and/or inactivation of the drug, or to the increased effect of CP on DBA/2 bone marrow resulting in damage to pre‐T cells that normally participate in thymus recovery.
Correlation between concentrations of n‐hexane and toluene in exhaled and environmental air in an occupationally exposed population
Authors: Periago J. Francisco , Morente Antonio , Villanueva Manuel , Luna Aurelio 
Published: October 2006

AbstractWe determined the correlations between the concentrations of n‐hexane and toluene in exhaled and environmental air in the shoe manufacturing industry. Data were collected in 1988 and in 1992 from a total of 265 subjects. Environmental air samples were collected with personal diffusive samplers by adsorption on activated charcoal during exposure and from end‐expired air (alveolar air) on cartridges of activated charcoal after exposure. Both compounds were desorbed with carbon disulphide and analysed by gas chromatography. Linear regression analyses showed a good correlation between environmental and end‐expired air concentrations (r = 0.82 for n‐hexane and r = 0.81 for toluene). These correlations allowed us to calculate the concentrations in expired air corresponding to current environmental limit values. The calculated concentrations in end‐expired air that correspond to current environmental threshold limit values of 176 mg m−3 for n‐hexane and 377 mg m−3 for tolueneare 28 mg m−3 (95% confidencelimit, 27–29 mg m−3) and 40 mg m−3 (95% confidence limit, 39–41 mg m−3), respectively. Similar correlations were found when the data from the two study periods were analysed separately.
Interactions of αNi3S2 with Guinea pig alveolar macrophages and liberation of inflammatory mediators
Authors: Teissier E. , Shirali P. , Hannothiaux M. H. , Marez T. , Haguenoer J. M. 
Published: October 2006

AbstractOur previous investigation presented evidence of interaction between αNi3S2 and membranous and cellular lipids of lung cells, resulting in significant increases in linoleic, linolenic and arachidonic acids. The present work was designed to follow the metabolic fate of arachidonic acid in αNi3S2‐exposed guinea pig alveolar macrophages (GPAM) in culture (50 μM αNi3S2 for 3 days).The metabolites of arachidonic acid were assessed by HPLC coupled with UV or electrochemical detection. The concentrations of malondialdehyde (MDA), hydroxyeicosatetraenoic acid (HETE), leucotrienes (LT) and reduced glutathione (GSH) were measured.In exposed cells a significant increase of MDA, a breakdown product of lipid peroxidation, was observed. In addition, the enzymatic reduction of 5‐hydroperoxyeicosatetraenoic acid (5‐HPETE) by the associated oxidation of GSH to GSSG increased 5‐HETE in GPAM cells and decreased GSH. 5‐Hydroperoxyeicosatetraenoic acid was furthermore converted to epoxides, such as leucotriene A4, and we also quantified in exposed cells a signficant increase of its subsequent catabolites LTB4, LTC4 and LTE4.Direct measurements of MDA and other metabolites of arachidonic acid clearly show that exposure of GPAM cells to αNi3S2 enhances lipid peroxidation. This lipid peroxidation is an autocatalytic free‐radical process and could be responsible for DNA damage. Furthermore, αNi3S2 intoxication induces the release of proinflammatory products, such as leucotrienes, and the decrease of glutathione.
An investigation of the main mutagenic components of a carcinogenic oil by fractionation and testing in the modified ames assay
Authors: Ingram A. J. , Scammells D. V. , May K. 
Published: October 2006

AbstractA low‐viscosity carcinogenic oil was extracted with dimethylsulphoxide (DMSO) and the extract fractionated into 1–3 ring aromatic components, 4–6 ring polycyclic aromatic compounds (PCAs) and polar materials. Each of these fractions was tested in the Mobil modified Ames assay at the same concentration as in the DMSO extract, alongside unfractionated DMSO extracts from the same oil and two reference oils. In addition the fractions were combined in various ways to examine inhibitory or additive effects.Clear positive findings were obtained with the DMSO extract of the main test oil, with some reduction in activity in a sample (the starting material for fractionation) that was back‐extracted to remove DMSO. Of the three fractions tested on their own and assessed in terms of mutagenicity index, the 1–3 ring aromatic fraction had the greatest mutagenic activity, showing similar activity to the starting material, whereas the 4–6 ring PCA fraction had much lower activity and the polar fraction showed the lowest activity with an absence of doubling in one of the tests.The polar fraction showed signs of an inhibitory effect on the response to the 1–3 ring aromatic fraction and to a questionable extent on that of the 4–6 ring PCA fraction. Although a low level of the 4–6 ring PCA fraction showed some inhibitory effect on the response to the 1–3 ring aromatic fraction, a low level of the 1–3 ring aromatic fraction added to the 4–6 ring PCA fraction enhanced the response.It was concluded that 4–6 ring PCAs were not the main mutagenic components of the oil examined and that therefore the mutagenic components may be different from the carcinogenic components. It was recognized, however, that there is a need for further data on the carcinogenicity of oil fractions, particularly relating to 1–3 ring aromatic compounds.
Evaluation of three antidotes on arsenic toxicity in the common earthworm (Lumbricus terrestris)
Authors: Li Wei , Chien Paul K. , Furst Arthur 
Published: October 2006

AbstractThe common earthworm (Lumbricus terrestris) is being evaluated in our laboratories as a substitute for mice in metal toxicity studies. These two disparate species have enzymes in common, such as catalase, superoxide dismutase and glutathione‐S‐transferase. Also, worms respond similarly to these rodents for selenium and nickel toxicity. Worms are less sensitive, however, to metal toxicity. In this study earthworms were challenged with three different arsenic compounds: arsenite, arsenate and the vesicant phenyldichloroarsine (PDA). The median lethal dose for each arsenic compound was determined. The order of toxicity of the arsenic compounds to the worms was PDA > arsenite > arsenate (24 h LD50 values were 189.5, 191.0 and 519.4 μmol kg−1, respectively). Individual mammalian dithiol antidotes, namely the sodium salt of 2,3‐dimercapto‐1‐propanesulfonic acid (DMPS), meso‐dimercaptosuccinic acid (DMSA) or 2,3‐dimercapto‐1‐propanol (BAL), were injected into the worms 5 min after various doses of the arsenic compound were administered. The decreases in acute toxicity values were recorded. All three antidotes protected the worms against arsenic toxicity with varying degrees of effectiveness. The protective action for the inorganic arsenic compounds was in the order DMPS > DMSA > BAL. For the organic arsenical, PDA, the most effective antidote was BAL.
Effects of single or repeated administration of a carbamate, propoxur, and an organophosphate, DDVP, on jejunal cholinergic activities and contractile responses in rats
Authors: Kobayashi Haruo , Sato Itaru , Suzuki Tadahiko , Matsusaka Naonori , Yuyama Akira , Akatsu Yasuhiko , Fujii Shin‐Ichiro 
Published: October 2006

AbstractWistar rats were injected once or repeatedly for 10 days with dichlorvos (DDVP, 5 mg kg−1), propoxur (10 mg kg−1), oxotremorine (0.1 mg kg−1) or atropine (5 mg kg−1). Animals were killed 20 min or 24 h after single or consecutive injections, respectively, for determinations of cholinergic activities and contractile responses to acetylcholine (ACh) of the jejunum. Single treatments: while DDVP and propoxur decreased acetylcholinesterase (AChE) activity, oxotremorine and atropine did not. Although DDVP, propoxur and oxotremorine increased levels of ACh, atropine decreased them. Contractile responses to ACh were enhanced by DDVP and reduced by oxotremorine and atropine. The Bmax value of binding of [3H]quinuclidinyl benzylate (QNB) to muscarinic ACh receptors was decreased by atropine. Consecutive treatments: DDVP and oxotremorine decreased AChE activity markedly and slightly, respectively. Although DDVP and oxotremorine increased levels of ACh, propoxur decreased them. Without affecting the contractile responses, DDVP caused a reduction and propoxur and atropine caused an increase in the Bmax value for binding of [3H]QNB. Both the contractile responses and the value of Bmax for binding of [3H]‐QNB were decreased by oxotremorine. In summary, propoxur and DDVP showed similar effects mainly through their anticholinesterase properties in the case of single injection, but DDVP had similar effects to those of oxotremorine and propoxur had similar effects to those of atropine in the case of repeated injection.
Distribution and urinary excretion of aluminium injected with several organic acids into mice: Relationship with chemical state in serum studied by the HPLC‐ICP method
Authors: Maitani Tamio , Kubota Hiroki , Hori Natsuko , Yoshihira Kunitoshi , Takeda Mitsuharu 
Published: October 2006

AbstractThe correlation between the in vivo tissue distribution or the urinary excretion of aluminium (Al) administered with four organic acids and the in vitro binding of Al to serum protein in the presence of the organic acids was studied. Aluminium was injected intraperitoneally into mice with an organic acid at a dose of 20 mg Al kg−1 (Al:ligand= 1:1 or 1:3). When the Al‐citrate mixture was administered, hepatic and renal concentrations of Al at 3 h were low, while hepatic Al concentrations for the other three organic acids (malate, tartrate and isocitrate) were considerably higher. Compared to the sole administration of Al, urinary excretion of Al was at a high level in all organic acids. Aluminium added in vitro to control serum as an Al‐citrate mixture was present only in a low‐molecular‐weight (LMW) fraction, while Al added with other organic acids was present in both the high‐molecular‐weight (HMW) and LMW fractions. Consequently, it was interpreted that Al in the LMW fractions was excreted into the urine and that a significant part of Al in the HMW fractions was transferred to the liver. The binding status of Al in serum observed in the in vitro study was also manifested in the in vivo samples obtained after the intravenous injection.
Effects of atrazine on reproductive performance in the rat
Authors: Šimić Branimir , Kniewald Jasna , Kniewald Zlatko 
Published: October 2006

AbstractThe effects of subacute exposure to atrazine on body weight, ovarian cycling, conception rate and the size of litters in Fischer strain rats were studied. An atrazine dose of 120 mg kg−1 body wt given p.o. daily for 7 days to both female and male rats caused statistically significant loss of body weight in both sexes during the period of treatment. After the cessation of treatment the body weight of female rats remained below control body weights at least for 2 weeks. In male rats the difference in body weights narrowed with time and reached control level 5 days after the last dose. Atrazine caused a significant increase in the relative weights of pituitary and prostate. Atrazine also transiently prolonged the oestrous cycle, characterized by extended vaginal dioestrus. As a result of disturbed ovarian cycling, the rate of successful mating decreased in the first week after treatment when both sexes were exposed or exposed females were mated with an unexposed male. No similar effect was observed when only the males were exposed. The size of litters did not differ significantly between experimental groups.
Urinary selenium excretion in workers with low exposure to mercury vapour
Authors: Ellingsen Dag G. , Nordhagen Hans P. , Thomassen Yngvar 
Published: October 2006

AbstractUrinary selenium excretion was studied in 21 mercury vapour (Hg°)‐exposed workers involved in the demolition of a chloralkali plant. The subjects had no known previous occupational exposure to mercury. Their mean pre‐exposure urinary mercury concentration, determined on average 1.2 days prior to the exposure, was 0.8 nmol mmol−1 creatinine (range 0.3–1.9). Their last mean urinary mercury concentration, determined on average after 51.4 days (range 19–103) of exposure, was 4.8 nmol mmol−1 creatinine (range 1.2–10.0). The exposure ceased on average 4.1 days after the last determined urinary mercury concentration. The corresponding concentrations of urinary selenium decreased from an average of 39.1 nmol mmol−1 creatinine (range 13.9–89.5) to 29.0 nmol mmol−1 creatinine (range 10.1–52.9) (P = 0.002). This finding may indicate that even a low to moderate work‐related exposure to Hg° may reduce the urinary selenium concentration in humans in a manner that is not yet fully known.
Detection of polycyclic aromatic hydrocarbon exposure damage using different methods in laboratory animals
Authors: Winker N. , Weniger P. , Klein W. , Ott E. , Kocsis F. , Schoket B. , Körpert K. 
Published: October 2006

AbstractBenzo[a]pyrene, benzo[b]fluoroanthene and dibenzo[a, h]anthracene dissolved in a 1:2 mixture of dimethylsulphoxide (DMSO) and water were administered to two groups of female mice, each group containing 15 mice. The doses were administered orally (via gavage) at the respective rates of 1 and 100 μg kg−1 body weight five times per week for a period of 9 weeks. The influence of the polycyclic aromatic hydrocarbons (PAHs) was determined using the following methods: determination of DNA‐PAH adducts, of chromosome injuries (micronucleus test), of induction of repair using the unscheduled DNA synthesis (UDS) test, and by examination of the DNA structure after nucleoid sedimentation. All the methods investigated provided evidence of a significant effect resulting from exposure to PAHs on the parameters examined. Following chronic exposure to PAHs, the formation of DNA‐PAH adducts and injury to the genetic material, as well as the appearance of micronuclei (micronucleus test), the induction of unscheduled DNA synthesis (UDS test) and mutation of the DNA structure (nucleoid sedimentation), were demonstrated. The described methods therefore provide a means for the detection of genetic damage caused by PAH exposure in humans.