bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aminoglutethimide as Second-line Hormonal Therapy in Advanced Breast Cancer: Response and Toxicity
Authors: Rowell N.P. , Gilmore O.J.A. , Plowman P.N. 
Published: December 2008

Seventy-nine postmenopausal patients received aminoglutethimide (AG; 750 mg daily) and hydrocortisone therapy for metastatic or locally recurrent breast cancer following the failure of other hormonal therapy. Fourteen of 64 patients, tolerating the drug and assessable for response, achieved a complete or partial response. Disease stabilisation occurred in a further 2 patients giving a response rate of 25% in these patients. Median duration of response was 10 months. Response rates to AG were not significantly different whether or not there had been a response to previous hormonal therapy but a trend to higher response rates in ER rich tumours was observed. Those with a longer interval from first relapse to the start of AG appeared more likely to respond. Side-effects were noted in 35 patients overall (44%) and in 70% of those over the age of 65 years. Treatment was discontinued because of toxicity in 10 patients and there was one death due to agranulocytosis. AG is active in postmenopausal breast cancer following failure of first-line hormonal therapy, toxicity limiting its use earlier in the disease.
Carbamazepine and Carbamazepine-10,11-epoxide Pharmacokinetics in an Overdose Patient
Authors: Patsalos P.N. , Krishna S. , Elyas A.A. , Lascelles P.T. 
Published: December 2008

1 A case report on a 13-year-old girl with idiopathic grand mal epilepsy who ingested 34 g carbamazepine (CBZ) and 80 mg clonazepam is presented.2 The patient survived but suffered severe temporary neurological toxicity characteristic of CBZ.3 CBZ was 79.6 ± 2.8% bound to serum protein and carbamazepine-10,11-epoxide (CBZ-E) binding was essentially concentration dependent.4 CBZ and CBZ-E elimination half-lives were 26 and 16.5 h respectively. An inhibitory metabolic interaction with the co-ingested clonazepam is suggested.
Evaluation of the BTS Approach to the Testing of Substances and Preparations for their Acute Toxicity
Authors: van den Heuvel M.J. , Dayan A.D. , Shillaker R.O. 
Published: December 2008

This study has shown that the new approach to acute oral toxicity testing proposed by the British Toxicology Society 1 provides the information on the toxic effects of materials necessary for human risk assessment, 2 can be used to rank materials for regulatory purposes on the basis of their acute toxicity, 3 provides advantages for animal welfare by requiring the use of fewer animals than conventional acute oral toxicity tests and by subjecting those animals used to less chance of experiencing pain or distress.
Accidental Poisoning in Childhood: A Multicentre Survey. 1. General Epidemiology
Authors: Wiseman H.M. , Guest K. , Murray V.S.G. , Volans G.N. ,   NPIS Monitoring Group
Published: December 2008

1 As background to a study of the effectiveness of packaging in preventing childhood poisoning, the National Poisons Information Service coordinated a prospective survey, in which 9 Accident and Emergency (A & E) departments and 5 paediatric departments, between July 1982 and February 1984, recorded 2043 cases of suspected accidental poisoning in children aged 0-60 months. 2 The products implicated were drugs (59%), household products (37%) and plants (3%). The drugs most frequently implicated were analgesics, anxiolytics, cough medicines, oral contraceptives and drugs to supplement diet or treat dietary disorders. The most frequently implicated household products were cleaners such as bleach, detergent and disinfectant, and petroleum distillate. 3 Seventy-five per cent of the children were 2 and 3-year-olds. Fifty-six per cent were male. 4 Only 22% of the children had signs or symptoms on admission. In only 2 cases were these serious. Treatment other than ipecacuanha and/or oral fluids was seldom required. Of the cases where outcome was recorded, 56% were discharged from A & E. The rest were admitted to a ward; only 7 children were admitted to intensive care units. No child died. 5 Comparison with HASS and other epidemiological surveys shows that these results are representative of national trends.
Studies on the Metabolic Behaviour of Industrial Actinide-bearing Aerosols after Deposition in the Rat Lung: An Experimental Basis for Interpreting Chest Monitoring Data and Assessing Limits on Intake for Workers
Authors: Stradling G.N. , Stather J.W. , Gray S.A. , Moody J.C. , Bailey M.R. , Hodgson A. , Collier C. 
Published: December 2008

The metabolism of 239Pu and 241Am in 3 site-specific industrial dusts has been studied after their deposition in the rat lung. A comparative experiment has also been carried out with a mixture of these actinides inhaled as their nitrates. The aim of this study was to provide an experimental basis for assessing limits on intake and to establish whether the 239Pu content in the lungs could be interpolated from measurements of 241Am. The results: 1 demonstrate the wide differences in the lung retention kinetics of the actinides and in the absolute and relative amounts translocated to the blood that can occur for industrially produced materials; 2 show that the annual limits on intake (ALIs) for the different materials vary between those postulated for class W and Y compounds by the International Commission on Radiological Protection; 3 indicate that acute intakes of 239Pu equivalent to the ALI can, depending on the nature of the dust, be estimated from 241Am chest monitoring data at times from a few days up to about 3 years after exposure.
A Case of Acute Poisoning with Fenitrothion (Sumithion)
Authors: Yoshida M. , Shimada E. , Yamanaka S. , Aoyama H. , Yamamura Y. , Owada S. 
Published: December 2008

A 56-year-old male attempted suicide by ingestion of about 60 ml of 50% fenitrothion (Sumithion) emulsion. Five hours later, combined hemoperfusion and hemodialysis (HP-HD) treatment was performed for 60 min and consequently the toxic symptoms improved gradually. However, cholinergic symptoms recurred 4 days after ingestion. Although HP-HD was immediately performed for 180 min, it had no effect on the clinical symptoms. He died of respiratory insufficiency 6 days after the ingestion of fenitrothion. Fenitrothion concentration in the organs and tissues showed the highest values in the fat tissue, followed in decreasing order by the pancreas, muscle, lung and brain. The results indicate that fenitrothion has high lipid solubility and deposits in the fat tissue. Furthermore, we believe that when HP-HD therapy is used in the treatment of acute insecticide poisoning it is important that it be performed continuously and in as early a stage as possible.
Exposure of the Skin to Methyl Bromide: A Study of Six Cases Occupationally Exposed to High Concentrations during Fumigation
Authors: Zwaveling J.H. , de Kort W.L.A.M. , Meulenbelt J. , Hezemans-Boer M. , van Vloten W.A. , Sangster B. 
Published: December 2008

1 The effects of exposure of the skin to high concentrations of methyl bromide were studied in 6 cases, who had been unintentionally exposed. 2 Exposure to high concentrations of methyl bromide (approximately 40 g/m3) for 40 min can lead to redness and blistering of the skin. This cannot be prevented by wearing standard protective clothing. 3 Skin lesions show a preference for relatively moist skin areas. 4 Plasma bromide levels were highest immediately following exposure (mean 9.0 ± 1.4 mg/l) and fell in subsequent hours (mean 6.8 ± 2.3 mg/l 12 h after the exposure), suggesting absorption of (methyl) bromide through the skin. 5 No systemic effects were noted in this series. 6 Fumigation with methyl bromide should not be done in such a way as to require the presence of workers inside closed areas, where methyl bromide is released.
Paraquat Poisoning by Skin Absorption: A Review
Authors: Smith J.G. 
Published: December 2008

All reported cases of paraquat poisoning by absorption through the skin are briefly reviewed. It is concluded that, while paraquat cannot be absorbed significantly through intact human skin, damage to the skin, either by paraquat itself or by other means, will permit greater systemic absorption and possibly poisoning. The lowest known concentration of paraquat to result in fatal poisoning through the skin is 5 g/l. Animal experiments with paraquat are also reviewed. The fact that the reported lethal dermal dose of paraquat in rats is slightly less than the oral dose is probably due to the lack of head restraint on the rats in the dermal dosing experiments. In vivo and in vitro tests on human skin at concentrations of 9 g/l and 5 g/l did not result in significant absorption of paraquat through the skin but in these experiments the skin was intact.
Blood Cadmium Concentrations in the General Population of British Middle-aged Men
Authors: Pocock S.J. , Delves H.T. , Ashby D. , Shaper A.G. , Clayton B.E. 
Published: December 2008

Blood cadmium concentrations were determined for 6919 men aged 40-59 randomly selected from general practice registers in 24 British towns. The mean and median blood cadmium were 1.9 and 1.4 μg/1 respectively and the distribution was highly skewed. The mean levels in non-smokers was 1.0 μg/l and current smokers showed a marked gradient with the daily amount smoked, with a mean of 3.9 μg/l in men smoking 40 or more cigarettes per day. Whereas 95% of men who never smoked had blood cadmium < 2.0 μg/l, 80% of men smoking 20 or more cigarettes a day exceeded this figure. 1% of the men had blood cadmium concentrations ≥ 7 μg/l virtually all of whom currently smoked cigarettes. Blood cadmium levels in ex-smokers were much lower than in current smokers even for those who had stopped within the past year. However, the mean levels in ex-smokers remained higher than the 'never smoked' for several years after stopping. There was little evidence that age, social class, or alcohol consumption were associated with blood cadmium levels after allowance for cigarette smoking. There is substantial geographic variation in mean blood cadmium for middle-aged men which could not be completely accounted for by smoking differences. Towns in the south and east of England all had mean levels under 2.0 μg/l whereas the majority of towns in other parts of Britain had mean levels greater than 2.0 μg/l. Possible reasons for this geographic pattern (e.g. geochemistry, industrial exposure, dietary differences) need further exploration.
Lead Toxicity on Endocrine Testicular Function in an Occupationally Exposed Population
Authors: Rodamilans M. , Osaba Ma J. Mtz. , To-Figueras J. , Fillat F. Rivera , Marques J. Ma , Pérez P. , Corbella J. 
Published: December 2008

The hypothalamo-pituitary-testicular axis was evaluated in a group of 23 men who worked in the lead smelting industry and had a history of occupational inorganic lead exposure. The endocrine status of the workers was related to lead poisoning biological markers. According to the duration of their lead exposure they were divided into three groups: group 1 < 1 year, n = 5; group 2 between 3 and 5 years, n = 8; group 3 > 5 years, n = 10.Serum testosterone (T), steroid binding globulin (SBG), free testosterone index (T/SBG), serum luteinizing hormone (LH), follicle stimulating hormone (FSH), Blood lead levels, and blood zinc protoporphyrin (ZPP) were measured in all workers.Groups 2 and 3 showed a decrease in serum testosterone levels, an increase in SBG levels, and a decrease in T/SBG index, suggesting a correlation between testicular dysfunction and duration of exposure. There was an increase in serum LH in group 1, which was not progressive. This suggests that prolonged lead exposure initially produces a direct testicular toxicity followed by hypothalamic or pituitary disturbance when longer periods of exposure take place.
The Effects of Soman on Human Isolated Uterine Arteries
Authors: Hu C.-Y. , Robinson C.P. 
Published: December 2008

1 The effects of soman on the resting contractile tension of human uterine arteries, and on contractions of these arteries to vasoactive agents were investigated. 2 Soman did not alter the resting tension of helically-cut strips of human uterine arteries. 3 Soman did not alter concentration-response curves of the strips to noradrenaline, serotonin, potassium chloride or histamine. 4 Soman increased contractile tension of human uterine artery strips to subsequently added 1 μM noradrenaline. 5 It is possible that this enhancement may be involved in decreased regional blood flow following soman administration.
Comparative Effects of Several Chelating Agents on the Toxicity, Distribution and Excretion of Aluminium
Authors: Domingo J.L. , Gómez M. , Llobet J.M. , Corbella J. 
Published: December 2008

The relative efficacy of citric, malic, malonic, oxalic and succinic acids, and deferoxamine mesylate (DFOA) on the toxicity, distribution and excretion in mice exposed to aluminium were compared. Chelating agents were administered intraperitoneally at a dose equal to one-fourth of their respective LD50. To determine the effect of the various chelators on the toxicity of aluminium, various doses of aluminium nitrate (938-3188 mg/kg) were administered intraperitoneally, followed by one of the chelators. Survival was recorded at the end of 14 days. Malic and succinic acids were the most effective. Malic acid and DFOA were the most effective in increasing the urinary excretion of aluminium. Citric acid was the most effective in increasing the faecal excretion of aluminium. Malonic, oxalic and succinic acids had no overall beneficial effects. Citric acid would appear to be the most effective agent of those tested in the prevention of acute aluminium intoxication. However, before the use of these compounds in human aluminium intoxication is possible, further investigations including the effects of these chelators after chronic aluminium intoxication are required.
The Toxic Effects of Alpha-Chloralose
Authors: Thomas H.M. , Simpson D. , Prescott L.F. 
Published: December 2008

1 Alpha-chloralose, formed by the condensation of glucose with chloral, is used as a rodenticide and in the control of bird pests. 2 In two cases of poisoning with alpha-chloralose the clinical features included coma and generalized convulsions resembling the effects of strychnine more than those of chloral hydrate. 3 The principles of management are the support of vital functions in the unconscious patient and removal of unabsorbed poison by gastric lavage. Diazepam may be used to control convulsions.
Acute MCPP Intoxication: Report of Two Cases
Authors: Meulenbelt J. , Zwaveling J.H. , van Zoonen P. , Notermans N.C. 
Published: December 2008

1 Two cases of serious intoxication with phenoxy herbicides (MCPP) are reported. 2 Both patients had central nervous system involvement, became unconscious and had an inadequate respiration. Muscle cramps and rhabdomyolysis with renal failure were noted in both. Shortly after admission both patients developed a serious decrease in arterial blood pressure (160/ 80 mmHg to 80/45 mmHg). In one patient this was demonstrated to be caused by a reduction in peripheral vascular resistance. 3 Plasma concentration of MCPP in patient 2 was 298 mg/l (3-4 h after ingestion). The plasma t½ was about 17 h. MCPP plasma elimination probably follows first-order kinetics.
Toxicity Testing: Some Principles and Some Pitfalls in Histopathological Evaluation
Authors: Roe F.J.C. 
Published: December 2008

. The aims of toxicity tests vary according to the use or proposed use of the substance to be tested. More knowledge about physiological and homeostatic control mechanisms will be needed before one can reliably distinguish between adaptive responses and toxic effects. More attention needs to be paid to quantifying the intrinsic sensitivity of certain methods used by toxicologists, particularly those with histopathological end-points. Much more attention should be paid than at present to seemingly beneficial effects of exposure o test materials since an understanding of these may throw useful light on mechanisms underlying oxic effects. Overfeeding gives rise to a wide variety of effects which impact in a major way on both general oxicity and oncogenicity end-points. Extrapolation to man usually involves the use of tumour incidence data to predict cancer Mortality in humans. Important new data on the effect of overfeeding on cancer incidence in rats Lged two years are presented. ' Complacency with regard to the relevance of rodent models for predicting toxicity for man is inwarranted.
Carcinogenicity of Chemicals: The Weight of Evidence
Authors: Carter R.L. 
Published: December 2008

. The evidence discussed here is derived from epidemiology, long-term bioassays in laboratory animals, and predictive short-term tests. Epidemiological data are obtained directly from human studies and are most compelling when hey demonstrate a large relative risk and a clear dose-response in association with a distinctive umour type. Exposure to a suspected carcinogen and the doses involved are, however, often difficult to determine, and the most sophisticated epidemiological methods are relatively insensitive. There are no epidemiological data for most occupational/environmental chemicals. Long-term bioassays can present major problems in design, interpretation and extrapolation. 'articular difficulties are associated with the planning of appropriate dose levels and the occurrence of certain tumours at high incidence in both control and test groups. Results from animal bioassays et priorities for concern and action but they cannot be reliably used for quantitative assessment of human risk. Evidence of potential carcinogenicity derived from short-term predictive tests, involving a wide variety of systems with diverse end-points, is increasingly important. Emphasis is placed on the teed for more in vivo procedures with a broadening of the scope of somatic cell targets.
Is Enzyme Induction Good for You? A Problem of Epidemiology and Toxicology
Authors: McLean A.E.M. 
Published: December 2008

1 The discoveries that pre-treatment with certain compounds could increase the amounts of drug metabolizing enzymes present in the liver and that metabolism could enhance as well as reduce the toxicity of exogenous molecules were important milestones in toxicology.2 Some clinically important adverse effects (vitamin D deficiency, reduced efficacy of oral contraceptives, interactions with anticoagulants) were found to be due to enzyme induction by, for example, anticonvulsants.3 Intestinal enzymes are also inducible and can respond rapidly to individual compounds while the liver enzymes respond more slowly to the diet as a whole. Although promoting hepatic tumours in rats and mice, phenobarbitone does not have this effect in man because there seems to be a threshold for promotion which human use does not exceed. In neither case is there evidence that reduction is harmful rather than adaptive in man.4 As to the future, post-marketing surveillance will continue to be important in assessing the safety of new products, and knowledge of the metabolism and pharmacokinetics of new compounds in experimental animals and in man will assume greater importance. Finally, greater understanding of intracellular processes will pave the way to the study of toxicology at the macromolecular level and thus to critically assess the validity of the animal models currently used in toxicity testing.
Occupational Toxicology
Authors: Carter J.T. 
Published: December 2008

1 Toxicology plays an important part in the prevention of work related disease. 2 The toxic effects of substances used at work are similar to those of other types of chemical, hence similar methods of investigation are used. 3 A very wide range of substances is used at work. The conditions of use determine the degree of exposure and the likelihood of adverse effects. 4 The scope for control of risks depends on a knowledge of likely adverse effects and the availability of technical and managerial means for reducing exposure. 5 The relationships between the employee, his employer, suppliers, expert advisers and the regulatory authorities determine the effectiveness with which toxic risks are identified and control measures implemented.
Nutritional Toxicology: The Significance of Natural Toxins
Authors: de Wolff A. 
Published: December 2008

The human diet may act as a carrier for substances which have a deleterious effect on human health either acutely or after chronic intake. These substances can be divided into nutrients, contaminants, food additives and natural toxicants. Recent research has mainly focused upon the contaminants and additives. This has led to regulatory measures which aim to prevent disease from exposure to such chemicals. The natural toxicants have not been as widely studied as the other classes of dietary toxins. Their possible impact on human health, however, justifies stimulation of research into this important branch of toxicology.
Clinical Toxicology - Past, Present and Future
Authors: Proudfoot A.T. 
Published: December 2008

1 The alarming increase in the incidence of self-poisoning in Western countries in the 1950s prompted the establishment of the National Poisons Information Service in the UK and the designation of certain Regional Poisoning Treatment Centres.2 The substances taken in acute poisoning episodes largely reflect the poisons available in the community and, in the UK at least, have changed with fashions in prescribing although psychotropic drugs and analgesics always predominate.3 Intensive supportive care with repeat-dose oral activated charcoal and even haemoperfusion has been proved effective in acute poisoning with central nervous depressant drugs such as barbiturates even though these latter drugs are now rarely encountered in overdose.4 Other advances in clinical toxicology include the introduction of the opiate antagonist naloxone, Fab antibody fragments for life-threatening digoxin overdosage and proven treatment for paracetamol poisoning. Analytical toxicology has also made a major contribution.5 On the debit side, formal psychiatric assessment of patients after acute poisoning remains contentious, tricyclic antidepressants are still a major problem and there is no effective treatment for poisoning with paraquat or for paracetamol when presentation is delayed.6 As to the future, although the 'epidemic' of serious acute poisoning of the 1960s and 70s appears to be past its peak, there will always be unusual and serious problems and the UK poisons information services must develop to make the best use of computer-based technology.
An Evaluation of the Safety of Ranitidine During Seven Years Daily Oral Administration to Beagle Dogs
Authors: Spurling N.W. , Selway S.A.M. , Poynter D. 
Published: December 2008

1 Ranitidine hydrochloride was administered orally to Beagles at doses equivalent to 50 mg once daily, or 5 mg twice daily, of ranitidine base/kg for more than 7 years. 2 Apart from looseness of faeces, seen mainly after doses of 50 mg/kg and only rarely after the first year of such treatment, there were no adverse clinical effects. There were no deaths related to treatment. 3 Periodic gastroscopy revealed nothing abnormal. 4 Peak plasma levels of ranitidine occurred within 2 h of dosing; levels were proportional to the doses administered. 5 There were no major differences in fasting plasma gastrin levels between treated and untreated dogs; the expected increase occurred in response to the provision of food and, predictably, this was greater following a dose of ranitidine. 6 A normal histamine-induced gastric secretory response was demonstrated. 7 Necropsy revealed no lesions of toxicological significance. Macroscopically the stomachs appeared normal but microscopic examination showed some gastritis in both treated and control dogs. No changes in enterochromaffin-like (ECL) cells were detected. Electron microscopy showed unimpaired secretory activity of parietal cells. 8 Thus, after more than 7 years administration to beagle dogs of doses in excess of the normal daily therapeutic dose, the stomachs showed no changes attributable to treatment and their secretory capacity was unimpaired.