bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elemental Mercury Vapour Toxicity, Treatment, and Prognosis After Acute, Intensive Exposure in Chloralkali Plant Workers. Part I: History, Neuropsychological Findings and Chelator effects
Authors: Bluhm Renata E. , Bobbitt Robert G. , Welch Larry W. , Wood Alastair J.J. , Bonfiglio J. Frank , Sarzen Christopher , Heath Andrew J. , Branch Robert A. 
Published: December 2008

Mercury poisoning occurred after the acute, prolonged exposure of 53 construction workers to elemental mercury. Of those exposed, 26 were evaluated by clinical examination and tests of neuropsychological function. Patients received treatment with chelation therapy in the first weeks after exposure. Eleven of the patients with the highest mercury levels were followed in detail over an extended period. Observations included the evaluation of subjective symptoms of distress, using the 'Symptom Check List 90-Revised' (SCL-90R) and tests of visual-motor function such as 'Trailmaking Parts A and B', 'Finger Tapping', 'Stroop Colour Word Test' and 'Grooved Pegboard.' On day 85 ± 11 (mean±s.d.) after exposure, these 11 men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L-penicillamine (NAP) in a short-term study designed to compare the potential to mobilize mercury and the incidence of drug-induced toxicity of these two chelating agents. Rapidly resolving metal fume fever was the earliest manifestation of symptoms. CNS symptoms and abnormal performance on neuropsychological tests persisted over the prolonged period of follow-up. There were significant correlations between neuropsychological tests and indices of mercury exposure. Serial mercury in the blood and urine verified the long half-life and large volume of distribution of mercury. Chelation therapy with both drugs resulted in the mobilization of a small fraction of the total estimated body mercury. However, DMSA was able to increase the excretion of mercury to a greater extent than NAP. These observations demonstrate that acute exposure to elemental mercury and its vapour induces acute, inorganic mercury toxicity and causes long-term, probably irreversible, neurological sequelae.
Pharmacokinetics of Fluazifop-butyl in Human Volunteers II: Dermal Dosing
Authors: Ramsey J.D. , Woollen B.H. , Auton T.R. , Batten P.L. , Leeser J.E. 
Published: December 2008

1 The absorption of the herbicide fluazifop-butyl (f-b), has been determined from plasma and urine measurements in groups of six male volunteers following dermal administration of 2.5, 25 and 250 ?g cm-2 from standardized formulations containing 0.05, 0.5 and 5.0% (w/v) fluazifop-butyl to a skin area of 800 cm2. 2 Urinary excretion rate of the principal metabolite fluazifop, following dosing with the 5% formulation, was described by a two-compartment pharmacokinetic model; the average elimination half-lives of initial and terminal phases were 18 h and approximately 70 h, respectively. For the other dose levels the elimination half-life was estimated to be 17 h; urine concentrations at later time points were too low to characterize a second compartment. 3 The estimated total fluazifop-butyl absorbed was 8.0, 3.4 and 1.6% of the applied dose for the 0.05, 0.5 and 5.0% formulations, respectively. 4 Up to 50% of the applied fluazifop-butyl was readily removed by skin washing and the majority of the remainder was transferred to clothing during the 24 h following application. 5 When six volunteers were given a daily dermal dose of the 0.5% formulation for five consecutive days, the plasma and urinary excretion kinetics of fluazifop could be accurately predicted by simple mathematical extrapolation of the kinetic data from the single exposure study at the equivalent daily dose. 6 It is concluded that fluazifop-butyl is only slowly and poorly absorbed through human skin and has a low potential to accumulate in man.
Chronic Low-Dose Exposure of Sodium Nitrite in VM-Strain Mice: Central Nervous System Changes
Authors: Hawkes C.H. , Cavanagh J.B. , Darling J.L. , Watkins B.A. , Thomas D.G.T. 
Published: December 2008

1 There is suggestive evidence that nitrite may be a causative factor in cerebral glioma. 2 To test this hypothesis we selected the VM mouse strain, known for its susceptibility to spontaneous glioma formation, and exposed 300 animals to 0.2% sodium nitrite in their drinking water. One hundred of this group were exposed both in utero and throughout their adult lives. The remaining 200 animals received nitrite from the time of weaning. A further 200 mice were used as controls and received distilled water. 3 All animals were maintained until their natural death and were then subjected to autopsy and routine histological examination. 4 There was no excess of nervous system tumours in the experimental groups.
Individual Differences in Activity of Glutathione Peroxidase and Catalase Studied in Monozygotic Twins Discordant for Smoking
Authors: Björkman Lars , Svartengren Magnus , Nordberg Monica 
Published: December 2008

1 Cigarette smoke contains free radicals. The enzymes glutathione peroxidase (GSH-px) and catalase are important parts of the anti-oxidative protecting system. 2 Ten pairs of monozygotic twins, who were discordant for smoking, were analysed in order to determine their erythrocyte glutathione peroxidase and catalase activities and their plasma concentrations of selenium. 3 Analysis of variance (ANOVA) revealed that the difference in activities of catalase and glutathione peroxidase was much less within pairs than between pairs, indicating a large individual variation due to genetic expression or shared environment and no major effect from smoking. 4 The plasma selenium levels of the investigated twins revealed sufficient intake of selenium to maintain maximal activity of GSH-px in erythrocytes. The mean±s.d. selenium concentration in plasma for smokers was 98 ± 16 μg 1-1 and for non-smokers 111 ± 16 μg 1-1. There was no correlation between plasma selenium and glutathione peroxidase in erythrocytes.
Sudden Infant Death Syndrome (SIDS) and the Toxic Gas Hypothesis: Microbiological Studies of Cot Mattresses
Authors: Kelley Joan , Allsopp Dennis , Hawksworth David L. 
Published: December 2008

1 Fifty infants' mattresses were studied to investigate the occurrence of viable fungal and bacterial propagules, with particular reference to Scopulariopsis brevicaulis which had been suggested to be implicated in SIDS cases. A total of 19 SIDS cases mattresses, 1 non-SIDS death, 20 used controls, and 10 new unused controls were examined. 2 Differences were found between SIDS and used controls in the variety of fungal species isolated and the numbers isolated from fillings; bacterial numbers were similar. 3 S. brevicaulis was isolated from only four mattresses, three of which were SIDS cases. It was not found in most of those on which death had occurred. 4 A number of potentially pathogenic or allergenic fungi, including Aspergillus fumigatus, were isolated more frequently from SIDS cases mattresses than new or used controls. 5 Scanning electron microscopy of mattress covers and fillings showed microbial 'biofilms' in the head areas of all SIDS cases examined. This was not seen on other samples. 6 The limited number of mattresses studied and the use of unmatched controls precludes the drawing of any general conclusions as to the significance of the biofilms or other fungi isolated. 7 Reports of the existence of a dimorphism in general growth forms of S. brevicaulis were investigated by growing and transferring authentic strains between a variety of growth media. 8 No 'slimy' state of this fungus was observed and dimorphism was not confirmed.
The No-Effect Level of Sodium Bromide in Healthy Volunteers
Authors: van Gelderen C.E.M. , Savelkoul T.J.F. , Blom J.L. , van Dokkum W. , Kroes R. 
Published: December 2008

1 A total of 0, 4 and 9 mg kg-1 body weight sodium bromide was administered orally to 45 healthy female volunteers. 2 The experiment lasted for six menstrual cycles: only during the first three cycles was bromide administered; 3 At the start, at the end of the administration period and at the end of the experiment a physical examination and haematological and routine clinical chemistry tests were performed. Except for nausea in relation to the intake of bromide, no adverse effects were observed. 4 The bromide concentration in plasma rose to 3.22 ± 0.93 mmol kg-1 in the 4 mg kg-1 group and to 7.99 ± 1.89 in the 9 mg kg-1 group by the end of the administration period. 5 Before and at the end of the experiment the thyroid hormones (T4, FT4, TBG, T3 and TSH) were analysed. No significant differences were observed between the groups. 6 Before, after three menstrual cycles and at the end of the experiment an EEG with a Visual Evoked Response was recorded. At the 4 and 9 mg kg-1 dose level in the α1-band and the β-bands significant changes were found (P < 0.1 and P < 0.05, respectively). The Visual Evoked Response showed no significant differences between the three groups. 7 From this experiment and previous experiments a no-effect level in humans for sodium bromide of 4 mg kg-1 body weight is proposed.
The Use of the Dog in Toxicity Tests on Pharmaceutical Compounds
Authors: Parkinson C. , Grasso P. 
Published: December 2008

1 The preclinical animal safety testing strategy used in pharmaceutical development is generally successful, with the large majority of new medicines not causing serious toxicity in man. The use of the dog has significantly contributed to this achievement by aiding the selection of safe compounds for human trials. 2 The dog should be selected as the non-rodent species for pharmacodynamic, pharmacokinetic, metabolic and other scientific reasons, not solely for practical considerations. 3 The dog is an extremely useful laboratory animal, particularly for procedures requiring extensive handling, detailed observation or biological sampling. 4 Refinements in the use of the dog have been achieved, but further progress is desirable. Retrospective analysis of pharmaceutical toxicity data could encourage the regulatory flexibility necessary for further progress.
Pentachlorophenol Carcinogenicity: Extrapolation of Risk from Mice to Humans
Authors: Reigner Bruno G. , Bois Frederic Y. , Tozer Thomas N. 
Published: December 2008

1 Pentachlorophenol (PCP) has been found to be carcinogenic in mice. The objective of this study was to extrapolate to humans the risk of cancer from data obtained in mice using information on disposition, serum protein binding and metabolism of PCP across species.2 A review of the literature indicates that neither PCP nor a mutagenic metabolite, tetrachlorohydroquinone (TCHQ), has been specifically identified as responsible for the carcinogenicity. In addition, the occurrence of TCHQ as a metabolite of PCP in humans is still questionable. Therefore, cancer risk assessment is performed on the assumption that PCP itself is responsible for the carcinogenicity.3 For interspecies extrapolation, a new method in which interspecies differences in clearance and serum protein binding are taken into account is used. The method gives estimates of equivalent human doses of PCP which are up to 4 times smaller than those obtained using body surface area. For both interspecies extrapolation methods, the estimated virtually-safe doses of PCP are smaller than the average daily intakes reported in groups of subjects nonspecifically exposed to PCP. Corresponding extra risks of cancer for lifetime exposure are from 20 to 140 times greater than the acceptable extra risk (10-6).The results obtained with this approach indicate that PCP is a possible public health hazard.
Hepatotoxicity Associated with Dietary Iron Overload in Mice
Authors: Omara Felix O. , Blakley Barry R. , Wanjala Lusimbo S. 
Published: December 2008

1 Weanling male CD-1 mice were fed 120 (control), 5000 and 8000 mg of iron kg-1 for seven weeks. The haematocrit ( P=0.265), water consumption ( P=0.170) and percentage body weight ratios of kidney, spleen and heart were not affected by iron supplementation. 2 Iron supplementation reduced weight gain ( P=0.023), increased weight of liver ( P=0.0001), the iron deposition index and concentration of iron in the liver ( P<0.01). A strong correlation between liver iron concentration and level of iron in the diet ( r=0.989) was observed. Histologically, the deposition of iron was restricted to the hepatocytes, Kupffer cells and splenic macrophages. 3 Consumption of 5000 and 8000 mg of iron kg-1 resulted in hepatic damage, as judged by elevated serum alkaline phosphatase and alanine aminotransferase activities ( P<0.05). 4 This study indicates that prolonged feeding of excess dietary iron has the potential to cause hepatic accumulation of iron with resultant liver toxicity, and that mice may be a suitable model to study the mechanisms of dietary iron overload.
The Role of Flumazenil in the Management of Patients With Acute Alteration of Mental Status in the Emergency Department
Authors: Chern Tzyh-Lih , Hu Sheng-Chuan , Lee Chen-Hsen , Deng Jou-Fang 
Published: December 2008

1 There are a few case reports which suggest that flumazenil can be used as a diagnostic tool in coma of unknown aetiology but no large scale studies have proved its efficacy and cost-effectiveness. 2 Fifty five patients with acute alteration of mental status of unknown aetiology were enrolled prospectively during a time period of one year. Flumazenil was injected intravenously in a regimen of 0.3 mg in the first minute followed by alternate 0.2 mg, 0.3 mg doses every minute until a total dose of 1 mg was given or until the patients responded. 3 Patients were divided into two groups based on their response to flumazenil: Group 1, responders and Group 2, non-responders. The hospital stay was shortened significantly and interventional procedures, such as CT of brain and endotracheal intubation, were rendered unnecessary in several patients in Group 1. The Group 1 patients had a more favourable outcome than that of Group 2. 4 We concluded that flumazenil may serve as a useful tool in diagnosis and management of carefully selected patients with acute alteration of mental status.
Amelioration of Cisplatin Toxicity in Rat Renal Cortical Slices by Dithiothreitol In vitro
Authors: Zhang J.G. , Zhong L.F. , Zhang M. , Ma X.L. , Xia Y.X. , Lindup W.E. 
Published: December 2008

1 The protective effects of dithiothreitol (DTT) on cisplatin-induced nephrotoxicity were investigated with rat renal cortical slices. 2 The nephrotoxic effects of cisplatin (2 mmol l-1) were manifested in several ways: the Na+ and water content were increased while K+ was decreased. The malondiadehyde (MDA) concentration in the slices and the lactate dehydrogenase (LDH) released into the medium were increased. The uptake of p-aminohippurate (PAH), the synthesis of glucose and the glutathione (GSH) concentration in the slices were all decreased. 3 Despite a DTT-related increase in platinum (Pt) uptake by the slices, DTT (0.5-2 mmol I-1 ) ameliorated all these toxic effects of cisplatin in a concentration related manner. 4 The results suggest that the protective mechanism of DTT is its antioxidative action, DTT is also a metal chelator, however, and so a protective effect via chelation of Pt by DTT cannot be excluded.
Comparison of Two Methods for Determining the Toxicokinetics of Fluazifop-butyl after Intravenous Dosing in Rats
Authors: Rawlings John M. , McLean Provan W. , Wilks Martin F. , Batten Peter L. 
Published: December 2008

1 We have described and compared the use of two blood sampling techniques to measure the kinetics of fluazifop-butyl, a selective herbicide. Following intravenous administration of radiolabelled compound, blood samples were collected from female rats either by tail vein puncture or from chronically implanted catheters inserted in tethered rats. Urine samples were also collected from tethered animals.2 Both techniques indicate that fluazifop-butyl is rapidly eliminated from blood into urine (t½3-4.5 h) and the overall blood concentration profiles were comparable between the two methods. However, by using cannulated rats, kinetic data were obtained from individual animals, providing. evidence of inter-animal variation and allowing compartmental and statistical analysis.3 The tethered rat technique is relatively simple and reliable. Compared to tail vein bleeding, results obtained from cannulated animals are more informative, providing comprehensive data from a small number of rats. It is therefore the preferred method for our kinetic based research studies using compounds known to exhibit multicompartmental elimination kinetics.
Bronchospasm Induced by Intravenous Adenosine
Authors: Drake I. , Routledge P.A. , Richards R. 
Published: December 2008

1 Adenosine is well known to cause bronchoconstriction when inhaled, but to date there has been only one report following the intravenous route. 2 Adenosine caused bronchoconstriction in two patients (the only two with asthma) out of 26 treated with the drug. In one subject the duration of response was much longer than previously reported following inhalation. 3 We suggest that adenosine may aggravate bronchospasm in some asthmatics and alternative treatments for supraventricular tachycardia should be considered in this group.
Human Volunteer Studies with Non-Pharmaceutical Chemicals: Metabolism and Pharmacokinetic Studies
Authors: Wilks M.F. , Woollen B.H. 
Published: December 2008

1 Human volunteer studies are an essential part of drug development but their use in the area of non-pharmaceutical chemicals has so far been very limited. Such studies can have considerable value in the assessment and improvement of the safe use of chemicals. 2 Once metabolic pathways and target metabolites have been identified in volunteers this information can be used in studies in the workplace or in the general population. Studies should be performed selectively only if there is both a toxic hazard and a significant exposure potential. In addition, they should only be carried out if the required information cannot be obtained in any other way. 3 Volunteer studies with non-pharmaceuticals have become increasingly acceptable in the light of established international guidelines, no-fault compensation, improvements in study design and technical developments which allow the use of very low dose levels. The final decision on whether to carry out a study must always rest with an independent ethical committee. 4 The practical aspects of the study should be specified in a detailed protocol conforming with the principles of good clinical practice. The safety of volunteers must be of paramount concern throughout. Depending on the nature of the chemical and the study, it may be advisable to carry out studies in a clinical facility where equipment is available for the treatment of any emergencies that might occur. 5 Numerous investigators have now shown that human volunteer studies are ethically acceptable, practicable and yield important information. The risk to volunteers is minimal and this approach can lead to an improved foundation for occupational hygiene standards, more accurate risk assessment and thus better protection of the workforce and the general population.
Prevalence of Food Additive intolerance
Authors: Madsen Charlotte 
Published: December 2008

1 The existing prevalence estimates of food additive intolerance1-4 are being reviewed. 2 In the EEC report the estimated frequency of food additive intolerance is 0.03% to 0.15% based on data from patient groups. 3 The British population study results in a prevalence estimate of 0.026%. The challenged population is 81 children and adults with a history of reproducible clinical symptoms after ingestion of food additives. 4 In the Danish population study a prevalence of 1-2% is found in children age 5-16. In this study a total of 606 children mainly with atopic disease have been challenged. 5 The prevalence estimates vary with a factor 100. As the results vary so do the study populations. 6 If the different study populations are accounted for, a common conclusion can be drawn: Food additive intolerance is found in adults with atopic symptoms from the respiratory tract and skin. The prevalence estimates are questionable but may be less than 0.15%. In adults and children with reproducible, and with more subjective symptoms, such as headache and behavioural/mood change the prevalence is even lower (0.026%). Food additive intolerance is primarily found in atopic children with cutaneous symptoms where the additive is aggravating an existing disease. The prevalence of food additive intolerance in children age 5-16 is 1-2%.
Pulmonary Protein Synthesis Response to Ozone
Authors: Kelly F.J. , Birch S. 
Published: December 2008

1 Exposure to either 800 or 1200 ppb ozone for 6 h did not influence the content or activity of mouse lung ribosomal RNA; in consequence pulmonary protein synthesis pathways were not altered. 2 Increasing the exposure period to 24 h had a marked effect on protein metabolism which depended on the dose of ozone employed. A dose of 800 ppb resulted in a 17% increase in lung protein content. Since both lung ribosomal capacity and fractional synthesis rates were unchanged at this time, it is concluded that both a lower ribosomal activity and an increased protein degradation rate were responsible for the decrease in content. 3 Exposure to 1200 ppb ozone for 24 h, paradoxically resulted in increases in both the fractional (33%) and total (19%) protein synthetic rates. These responses were due to an increased pulmonary ribosomal efficiency in the lung at this time. 4 We conclude that, in the short term, reduced pulmonary synthetic capacity is not a component of ozone-induced lung injury, but rather, this important component of the repair mechanism, can be up-regulated in response to lung injury.
Advantages and Disadvantages of Using Human Cells for Pharmacological and Toxicological Studies
Authors: Hawksworth Gabrielle M. 
Published: December 2008

1 Marked species differences in the distribution and affinity of drug receptors, and in the patterns of biotransformation and susceptibility to the toxicity of xenobiotics, provide the impetus for using human tissues for pharmacological and toxicological studies.2 Studies with intact cells facilitate the correlation of xenobiotic metabolism with cellular indices of toxicity, which can provide the mechanistic basis for understanding species differences in toxicity.3 Human cells in suspension or primary culture reflect the variability in susceptibility to toxicity in a population.4 The current limitation to these studies is scarcity of human material, the need for improved (cryo)preservation techniques for human hepatocytes/precision-cut slices and difficulties in predicting in vivo exposure-risk relationships from in vitro dose-response relationships.