bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Ranitidine Fails to Suppress the Growth in vitro of Haemopoietic Progenitors from Human Peripheral Blood or Bone Marrow
Authors: Reid C.D.L. , Kirk A.
Published: December 2008

Ranitidine was added in various concentrations (25-1600 ng/ml) to clonal assays of haemopoietic progenitors of normal human peripheral blood or bone marrow. Although a significant reduction in colonies forming from granulocyte-macrophage progenitors (CFU-GM) was demonstrated at the lowest drug concentration, no significant growth suppression was seen at higher concentrations. There was no evidence for growth inhibition of either erythroid progenitors (BFU-E) or pluripotent progenitors (CFU-mix) at any of the drug concentrations studied. A direct toxic effect of ranitidine on normal haemopoietic progenitors thus appears an unlikely cause of cytopenias observed during treatment.
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.
Metoprolol α-Hydroxylation Polymorphism in the San Bushmen of Southern Africa
Authors: Sommers De K. , Moncrieff J. , Avenant J.
Published: December 2008

1 The metabolic oxidation of metoprolol has been studied in a group of 98 San Bushmen.

2 The amounts of metoprolol and α-hydroxy metoprolol excreted in 0-8 h urine collection, after dosing with 100 mg metoprolol, were measured and the metabolic ratio (% dose excreted as metoprolol/% dose excreted as α-hydroxy metoprolol) calculated.

3 Frequency distribution and probit plots of the metabolic rate data showed a bimodal distribution with 4.1% of the population exhibiting slow metabolism with an MR > 10.

4 These results are much less than found in Caucasians (8.4%) but very different from the unimodal distribution found for Nigerians.

5 A previous study in the same group of Bushmen had revealed that 18 of 96 subjects were poor or non-metabolizers of debrisoquine to 4-hydroxy debrisoquine, but only one of the poor metoprolol metabolizers was a poor metabolizer of debrisoquine.

6 On the basis of these results, the claim of debrisoquine type of polymorphism for β-adrenoceptor antagonists found in Caucasians cannot be extrapolated to the San Bushmen, and one must query the use of debrisoquine as measure of oxidative status in any group other than Caucasians.
Hyperaluminaemia Associated with Oral Citrate and Aluminium Hydroxide
Authors: Kirschbaum B.B. , Schoolwerth A.C.
Published: December 2008

1 A hospitalized patient with renal failure receiving oral aluminium hydroxide was found to have a blood aluminium level of 3124 μg/l (116 μmol/l) .

2 The extremely high aluminium concentration was attributed to the concurrent use of an oral citrate solution which converted the aluminium to a more soluble and absorbable form.

3 The combination of oral aluminium and citrate should be avoided in patients with poor renal function.
Immunotherapy for the Treatment of Acute Paraquat Poisoning
Authors: Nagao M. , Takatori T. , Wu B. , Terazawa K. , Gotouda H. , Akabane H.
Published: December 2008

For the purpose of sequestering paraquat in the plasma compartment and preventing it from accumulating in tissues the effects of intravenous administration of anti-paraquat antibodies to rats were studied. After an intravenous paraquat injection of 0.1 mg/kg, the plasma paraquat concentration from rats pretreated with anti-paraquat antibodies was significantly increased and the amount of paraquat excreted in urine was significantly decreased compared to the control group. The concentration of paraquat in bile and organs except liver, was not changed by the treatment, but the paraquat level in the liver was significantly increased. Although immunotherapy succeeded in sequestering paraquat in the plasma compartment, it could not prevent paraquat from accumulating in tissues.
The UK Blood Lead Monitoring Programme 1984-1987: Results for 1986
Authors: Quinn M.J. , Delves H.T.
Published: December 2008

The Department of the Environment (DOE) undertook an extensive programme to monitor blood lead concentrations annually over the period 1984 to 1987 in the context of the reduction in the maximum permissible lead content of petrol from 0.4 to 0.15 g/l from 1st January 1986. Blood samples (all venous) were analysed for lead by atomic absorption spectrophotometry (AAS); considerable efforts were made to ensure the validity of the analytical results.

In 1986, emissions from petrol driven vehicles effectively fell by 60% and air lead concentrations fell by just over 50%. Against the background of a long-term downward trend in blood lead concentrations of 4-5% per year, there were average falls in blood lead in 1986, compared with 1985, of around 1 μg/100 ml (9-10%) for adults in both 'exposed' and 'control' groups; about 2 μg/100 ml (18%) in traffic police; and about 1.5 μg/100 ml (16%) in children. Levels fell in 1986 in all age groups, in all social classes, and in all categories of smoking and drinking habits, age of dwelling and length of residence.

Exposure to lead from a number of sources was being reduced simultaneously; blood lead concentrations probably fell in both 1985 and in 1986 for reasons additional to the reduction in the lead content of petrol. For children, petrol lead appeared to have been made a slightly larger contribution to the body burden than for adults.
Effect of Theophylline and Salbutamol on Hepatic Drug Metabolism
Authors: Døssing M. , Evald T. , Lange P. , Christensen H.R.
Published: December 2008

Fifteen otherwise healthy asthmatics with reversible airway obstruction were treated with salbutamol (8 mg slow release twice daily) and theophylline (300 mg twice daily). Each drug was administered for 4 weeks in a double-blind randomized crossover trial.

Irrespective of which drug was given first, salbutamol increased antipyrine clearance significantly by a factor of 1.10 and 1.15 after 2 and 4 weeks of treatment, respectively. Theophylline did not change antipyrine clearance.

There was no correlation between the extent of change in antipyrine clearance during either of the drug treatments and alterations in lung function as assessed by changes in peak flow, forced vital capacity and forced expiratory volume in first second.
Pharmacokinetic Interaction Between Indoramin and Ethanol
Authors: Abrams S.M.L. , Pierce D.M. , Johnston A. , Hedges A. , Franklin R.A. , Turner P.
Published: December 2008

1 The effect of ethanol consumption (0.5 g/kg) on the pharmacokinetics of the alpha adrenoceptor antagonist indoramin, administered orally (50 mg) or intravenously (0.175 mg/kg) has been investigated in young volunteers. Sedation was also assessed using a visual analogue scale.

2 After oral indoramin administration, ethanol caused increases of 58% (P <0.01) in CPmax , and 25% (P <0.05) in AUC. There was no effect of alcohol on elimination half-life. The combination of ethanol and indoramin was more sedative than indoramin alone.

3 Ethanol did not alter the pharmacokinetics of an intravenous dose of indoramin. However indoramin caused a small but statistically significant increase (26%) in blood ethanol concentrations during the first 1.25 h after dosing. Both indoramin and ethanol caused sedation.

4 The increased bioavailability of oral indoramin in the presence of ethanol may reflect some enhanced absorption, but it is also consistent with inhibition of first-pass metabolism of a flow-limited drug. The clinical implications are discussed.
Use and Abuse of Volatile Substances in Industry
Authors: Parker S.E.
Published: December 2008

1 Although there are trends towards the use of 'safer' or non-solvent materials, the overall consumption of solvents will probably not change very much over the next few years. Substitution of solvents by 'safer' materials is a complex and difficult process and the rate of change is correspondingly slow.

2 HSE exposure data show that generally industry controls most solvent use quite well. High personal exposures are not widespread and tend to occur in a fairly small number of premises involving 'end user' processes (mixing, spraying, etc).

3 Exposure in industry is generally to mixtures of solvents rather than single substances. The degree to which abuse is a contributory factor in exposure is uncertain, but there is probably greater opportunity for abuse to occur in 'end user' processes.

4 The experience of the author and colleagues in the HSE supports the evidence for the occurrence of volatile substance abuse (particularly of organic solvents) in industry but the extent of the practice is not known.

5 The proposed Control of Substances Hazardous to Health Regulations (COSHH) will bring greater emphasis on the assessment of risks to health in industry, which must include the potential for abuse, together with appropriate training and supervision.
Volatile Substance Abuse: Evaluation and Treatment
Authors: Richardson H.
Published: December 2008

1 A scheme for the identification and evaluation of volatile substance abusers is outlined which emphasizes the need for medical history, drug history, emotional/behavioural and dependency questionnaires and physical examination.

2 Poor initial evaluation may lead to non-recognition of dependent abusers who may present later with more serious problems.

3 Suggestions for prevention and treatment of chronic abusers are discussed and some advice for parents is outlined.
Hyponatraemia during Oxcarbazepine Therapy
Authors: Pendlebury S.C. , Moses D.K. , Eadie M.J.
Published: December 2008

A clinical and pharmacokinetic study was carried out progressively substituting a new anticonvulsant oxcarbazepine for its congener carbamazepine in a group of patients with refractory epilepsy. Although oxcarbazepine showed possible though not statistically significant advantages of better seizure control and was probably less sedating, its use was associated with a dose-dependent reduction in plasma sodium levels in 12 of 15 patients. The mean plasma sodium level fell from 137.5 ± 5.2 (s.d.) to 128.5 ± 6.1 mE/1. Imposed restriction of fluid intake may have minimized the degree of hyponatraemia. This adverse effect may limit the role of the drug as an anticonvulsant or necessitate special precautions when it is used. However, the possibility of employing the drug in diabetes insipidus may be worth exploring.
Rhabdomyolysis and Acute Renal Failure Induced by Paraphenylenediamine
Authors: Averbukh Z. , Modai D. , Leonov Y. , Weissgarten J. , Lewinsohn G. , Fucs L. , Golik A. , Rosenmann E.
Published: December 2008

1 We present a 40-year-old healthy man who developed a typical clinical picture of rhabdomyolysis following the administration of paraphenylenediamine by a witchdoctor as a pain killer.

2 Two groups of 15 mice were given paraphenylenediamine 70 mg/kg and 35 mg/kg respectively. Biochemical and histological findings of rhabdomyolysis developed in both groups, without kidney damage.

3 Paraphenylenediamine may cause rhabdomyolysis resulting in acute renal failure in humans. In mice, however, it produces rhabdomyolysis, but the kidneys are not affected.
Cytotoxic Effects of Trimethyltin Chloride on Human Peripheral Blood Lymphocytes in vitro
Authors: Ghosh B.B. , Talukder G. , Sharma A.
Published: December 2008

Trimethyltin chloride was found to induce cytotoxic damage in vitro in human peripheral blood lymphocytes. Two concentrations (0.5 μg and 1.0 μg) were added to lymphocytes from male and female subjects in mitogen stimulated and serum supplemented culture medium for 72 h. A dose-related increase of inhibition of replication index (P < 0.01) and cell division (P < 0.001) was observed. The frequencies of abnormal cells and chromosomal aberrations such as chromatid and chromosome breaks, dicentrics, triradial and quadriradial configurations were increased significantly (P < 0.001), as were micronucleus counts (P < 0.001) and sister chromatid exchanges (P < 0.001). Endoreduplication, an extremely rare spontaneous event in human lymphocytes, was observed in a few cases at all dose levels. The effects were more pronounced in lymphocytes obtained from habitual smokers.
Methaemoglobin Production and Reduction by Methylene Blue and the Interaction of Methylene Blue with Sodium Nitrite in vivo
Authors: Marrs T.C. , Bright J.E. , Inns R.H.
Published: December 2008

Methylene blue, at high concentrations, interferes with the estimation of methaemoglobin using the IL 282 CO-oximeter: the dye does not interfere with the method of Evelyn & Malloy for determination of methaemoglobin. In beagle bitches methylene blue causes both methaemoglobinogenesis and methaemoglobin reduction, the effect of the former being to delay the decline of methaemoglobin levels, when methylene blue is used to reverse the methaemoglobinaemia produced by sodium nitrite.
Non-correlation between Debrisoquine and Metoprolol Polymorphisms in the Venda
Authors: Sommers De K. , Moncrieff J. , Avenant J.
Published: December 2008

1 The metabolic 4-hydroxylation of debrisoquine has been studied in a group of 98 black African villagers in Vendaland.

2 The metabolic α-hydroxylation of metoprolol has been studied in 94 of the same black African villagers.

3 A 4% prevalence of poor oxidative metabolism of debrisoquine and a 7.4% incidence of poor oxidation of metoprolol were found. The 4% result for debrisoquine differs considerably from the 19% found in San Bushmen, 30% in Hong Kong Chinese, 9% in Britains and 0% in Nigerians and Japanese, whilst the 7.4% result for metoprolol compares with 8.4% in Britains but differs from 0% in Nigerians and 4.1% in San Bushmen.

4 None of the poor oxidative metabolizers of debrisoquine were also poor oxidative metabolizers of metoprolol. This is contrary to results in British and Nigerian subjects where defective oxidation of metoprolol co-segrates with that of debrisoquine.

5 No similarities were found between the Venda metabolic ratio (MR) distributions and either extensive or poor MR distributions in Britains or Nigerians.
Assessment of Toxicity for Major Hazards: Some Concepts and Problems
Authors: Illing H.P.A.
Published: December 2008

Approaches to the assessment of the toxic effects which may arise from chemical Major Hazards are examined. The definitions of hazard and risk and the types of toxicity data required for risk analysis are investigated with particular reference to the quality of the data and models available.
Fatal Phenolphthalein Poisoning with Fulminant Hepatic Failure and Disseminated Intravascular Coagulation
Authors: Sidhu P.S. , Wilkinson M.L. , Sladen G.E. , Filipe M.I. , Toseland P.A.
Published: December 2008

A 32-year-old female ingested an unknown quantity of Nylax tablets containing phenolphthalein. This results in widespread organ involvement, predominantly causing liver damage and disseminated intravascular coagulation. The eventual cause of death was massive liver necrosis. We suggest that phenolphthalein was responsible for the widespread damage.
Influence of Nutritional Factors on 239Np and 233Pa Retention in Weanling Rats
Authors: Kargacin B. , Volf V.
Published: December 2008

The estimated intestinal absorption after a single administration of 239NR-nitrate to fasted weanling rats (about 2% of the oral dose) was ten times higher than that of 233Pa administered as the chloride. Rats drinking tomato juice, apple juice or tea instead of water had a similar retention to the control group. However, when a small amount of tea was administered immediately before 239Np, the absorption and retention values were six times lower. When animals received only milk or glucose, the whole body retention of 239Np and 233Pa increased about 20 and 200-300 times, respectively, due mainly to a very high retention in the large intestine. When rats were fed milk plus rat chow, the whole body and gut retention of 233Pa was only two and three times higher, respectively; in the other organs less 233Pa was found than in control animals. This indicates that the extremely high retention of radionuclides in the gut contents of young rats fed only milk is temporary and disappears when solid food is available.
Monitoring of Patients taking Canthaxanthin and Carotene: An Electroretinographic and Ophthalmological Survey
Authors: Arden G.B. , Oluwole J.O.A. , Polkinghorne P. , Bird A.C. , Barker F.M. , Norris P.G. , Hawk J.L.M.
Published: December 2008

1 Patients who have taken canthaxanthin and beta-carotene to avert phototoxicity have been monitored by electroretinographic testing.

2 Patients took the compounds only during the summer months, but were monitored for more than 1 year to determine if seasonal changes in the ERG were visible.

3 The characteristic refractile retinal crystals reduced during the winter.

4 The scotopic b-wave amplitude increased during the winter, whether evoked by red or blue flashes.

5 No other ERG parameter altered.

6 Changes noted in 3 and 4 above are reversible.

7 A dose/ERG-amplitude response relationship was established, but no correlation between blood level or total cumulative dose and b-wave amplitude could be found.

8 It is suggested that the Müller cells concentrate canthaxanthin and this is the mechanism which affects the ERG.
Toxicological Data after Heroin Overdose
Authors: Kintz P. , Mangin P. , Lugnier A.A. , Chaumont A.J.
Published: December 2008

Capillary gas chromatography with selective nitrogen detection was employed to quantify morphine and 6-monoacetylmorphine in biological fluids and tissues in five deaths attributed to heroin injection overdose. The minimum lethal concentration found was 0.021 μg morphine per ml of blood. In all cases, 6-monoacetylmorphine was identified in urine, confirming heroin abuse.
Intracellular Localization of Cerium. A Microanalytical Study using an Electron Microprobe and Ionic Microanalysis
Authors: Berry J.P. , Masse R. , Escaig F. , Galle P.
Published: December 2008

Radioactive cerium is a nuclear toxicant. Metallic cerium is used in industry. Aspects of the intracellular metabolism of this element were studied following intraperitoneal injection and aerosol exposure in rat. Two microanalytic methods, an electron microprobe and ionic microanalysis, enabled the sites of incorporation and the process of intracellular concentration of cerium to be determined in the liver, lung, kidney, bone marrow and bone tissue. The very high sensitivity of ionic analysis enabled very low concentrations of cerium to be detected with a spatial resolution of 0.5 μm. Microanalysis by electron microprobe permitted: (i) the lysosomal localization of cerium to be determined; and (ii) the lysosomal coprecipitation of cerium with phosphorus to be demonstrated. Results are discussed in relation to aspects of radiological protection.
Toxicokinetics of Paraquat in Humans
Authors: Houzé P. , Baud F.J. , Mouy R. , Bismuth C. , Bourdon R. , Scherrmann J.M.
Published: December 2008

1 The toxicokinetics of paraquat were studied in 18 cases of acute human poisoning using a specific radioimmunoassay. Plasma paraquat concentration exhibited a mean distribution half-life ( t½ α) of 5 h and a mean elimination half-life ( t½ β) of 84 h. Cardiovascular collapse supervened early during the course of the intoxication and was associated with the distribution phase. Death related to pulmonary fibrosis occurred late and was associated with the elimination phase.

2 Pharmacokinetic analysis of urine paraquat excretion confirmed the biphasic decline of paraquat. Moreover, renal paraquat and creatinine clearances were not correlated but renal paraquat clearance was never higher than the renal creatinine clearance.

3 Tissue paraquat distribution was ubiquitous with an apparent volume of distribution ranging from 1.2 to 1.6 l/kg. Muscle could represent an important reservoir explaining the long persistence of paraquat in plasma and urine for several weeks or months after poisoning.
The Role of Thorium in Endomyocardial Fibrosis
Authors: Singh N.P.
Published: December 2008

The behaviour of thorium in animals exposed through injection, ingestion and inhalation, as well as in uranium miners, millers and the general population suggests that thorium . accumulates primarily in the lung, tracheobronchial lymph nodes and skeleton; or in the liver if injected with polymeric thorium. Epidemiological studies on uranium miners, Thorotrast studies in man and animal, and studies on the toxic effects of thorium in animals suggest that there is no apparent heart diseases due to exposure to thorium in man and animal.
Occupational Cadmium Exposure and Testicular Endocrine Function
Authors: Mason H.J.
Published: December 2008

Cadmium is known to cause testicular necrosis in several animal species, although there is little data on its possible effects in humans. We have investigated the effect of occupational cadmium exposure on the pituitary-testicular endocrine axis, as measured by serum testosterone, luteinizing hormone (LH) and follicular-stimulating hormone (FSH), in a well-characterized population occupationally exposed to cadmium. Over 60% of all workers, who had been exposed to cadmium oxide fumes for longer than a year, in a single factory, since 1926, were studied. Integrated cadmium exposure estimates were constructed for each subject from atmospheric measurements, together with other available company data, and these exposure estimates were validated by in-vivo neutron activation analyses of liver cadmium burdens. The lack of testicular endocrine effects was in contrast to significant dose-related changes in renal glomerular and tubular function demonstrated in the same population.
Zolpidem Intoxication Mimicking Narcotic Overdose: Response to Flumazenil
Authors: Lheureux P. , Debailleul G. , De Witte O. , Askenasi R.
Published: December 2008

Zolpidem is a recently introduced sleep-inducer which is thought to act on the central-type benzodiazepine receptors. This observation is the first report of drug poisoning with this compound. The toxic response was characterized by the development of a profound but short-lasting coma, associated with pin-point pupils and respiratory depression, as observed in a narcotic overdose. These clinical signs were not influenced by the administration of naloxone, but responded dramatically to flumazenil. Some analytical data on zolpidem toxicokinetics are presented.
Extracorporeal Regional Complexing Haemodialysis Treatment of Acute Inorganic Mercury Intoxication
Authors: Kostyniak P.J. , Greizerstein H.B. , Goldstein J. , Lachaal M. , Reddy P. , Clarkson T.W. , Walshe J. , Cunningham E.
Published: December 2008

A 70-year-old white female presented approximately 24 h after ingesting three 475 mg tablets (1.425 g) of mercuric chloride in a suicide attempt. Acute renal failure necessitated the initiation of haemodialysis approximately 4 d after the ingestion. Treatment with BAL (2,3-dimercaptopropanol) resulted in only small increases in mercury output into dialysate. A new procedure involving the extracorporeal infusion of the chelating agent dimercaptosuccinic acid (DMSA) into the arterial blood line during haemodialysis was initiated. This procedure of Extracorporeal Regional Complexing Haemodialysis (ERCH) had been effective in increasing methylmercury removal in patients poisoned by contaminated grain. The first DMSA-ERCH procedure was performed 6 d after poisoning. There was a dramatic increase in mercury output into the dialysate. During three treatment sessions of 80 min each, 1189 μg of mercury were removed from the patient. The dialysed mercury represented the only mercury output since the patient was anuric and not producing faeces. DMSA-ERCH appears to be much more effective than BAL and haemodialysis in the treatment of acute inorganic mercury poisoning. The long interval between poisoning and initiation of treatment probably contributed to the patients ultimate demise, 28 d after poisoning. Efficacy of the DMSA-ERCH procedure for inorganic mercury poisoning is likely to be improved as the interval between exposure and treatment is reduced.
High Serum Concentrations of Aflatoxin in Nepal as Measured by Enzyme-Linked Immunosorbent Serum Assay
Authors: Denning D.W. , Sykes J.A. , Wilkinson A.P. , Morgan M.R.A.
Published: December 2008

1 Sera from 28 Nepalis, both patients and workers in a hospital in Banepa, Nepal were examined for AFB1 by enzyme-linked immunosorbent assay (ELISA).

2 This assay, previously validated using spiked sera, provides a sensitive rapid determination of serum aflatoxin (B1, G1 and Q1).

3 All 28 sera were positive with concentrations from 60 pg ml-1 to 10 ng ml-1 .

4 These results suggest that consumption of aflatoxin in Nepal is high (> 50-800 ng kg -1 d-1).

5 No reports of the degree of contamination of food, human consumption or body fluid concentrations of aflatoxin in Nepal have been previously published.

6 Aflatoxin may contribute to the development of hepatocellular carcinoma, which is probably a common tumour in Nepal.
Paracetamol Poisoning in Pregnancy: An Analysis of the Outcomes of Cases Referred to the Teratology Information Service of the National Poisons Information Service
Authors: McElhatton P.R. , Sullivan F.M. , Volans G.N. , Fitzpatrick R.
Published: December 2008

A study was carried out to investigate the outcome of pregnancy in 115 women who had been exposed to paracetamol overdose. Follow up was obtained in 48 cases. Exposure occurred in all trimesters, and the most striking feature of this series is that the majority of the pregnancy outcomes were normal. None of the mothers died. There were 39 live born infants with no malformation, 14 of whom had been exposed in the first trimester. Four babies, exposed in the third trimester had neonatal problems, but these seem unrelated to paracetamol. There were two live born infants with gross malformations (spina bifida occulta; and cleft lip and palate). However, as the overdoses occurred at weeks 26 and 28 respectively, long after the structural development of these organs, the malformations could not have been caused by the paracetamol. There were two spontaneous abortions, both in the first trimester, which occurred two weeks after the overdose which may be related to the paracetamol. The overall conclusion is that paracetamol overdose per se is not necessarily an indication for termination of pregnancy.
Two Cases of Organophosphate Poisoning with Development of Intermediate Syndrome
Authors: Karademir M. , Ertürk F. , Koçak R.
Published: December 2008

Two cases of intermediate syndrome caused by organophosphorus poisoning are reported. Trichlorfon, propoxur (a carbamate pesticide) and fenthion were ingested in both attempts at suicide. After successful conventional therapy during the cholinergic phase, but before the time when the onset of delayed neuropathy might be expected, an intermediate syndrome developed. It affected the proximal limb muscles, neck flexors and respiratory muscles 2 d after pesticide ingestion. The two patients needed respiratory support. Recovery from the intermediate syndrome was complete in both patients, although one subsequently developed delayed neuropathy.
Computerized Product Information System: The Toxicological Index
Authors: Lapointe G. , Larue M. , Baril M.
Published: December 2008

The Toxicological Index, a division of the Commission de la Santé et de la Sécurité du Travail, was established in 1980 by the Quebec Government. Its main objective, as a database producer, is to provide health and safety related toxicological information to anyone who is involved in risk management in the workplace. In order to meet this requirement, a fully computerized information system was created. It has allowed us to process, over the past 5 years, 250,000 information inquiries, to register 100,000 contaminants, to exchange information with 3,300 product manufacturers and to provide our users with 6,500 fully reviewed toxicological information profiles. The procedure used to assess the information as well as the choices made to achieve our objective in terms of quantity and quality of the information provided are described.
Influence of 5- Hydroxymethylfurfural (5-HMF) on the Overall Metabolism of Human Blood Cells
Authors: Nässberger L.
Published: December 2008

5-Hydroxymethylfurfural (5-HMF) is a major breakdown product occurring in high concentrations in fructose and glucose solutions. Most of its formation occurs during autoclaving but spontaneous breakdown also takes place. We incubated human blood cells (granulocytes, erythrocytes and thrombocytes) with 5-HMF in the following concentrations 73.5, 735 μM and 7.35 mM. Heat output was increased in erythrocytes at the highest concentration by about 60%. An adverse effect was seen in granulocytes where a statistically significant reduction in heat output, of about 17%, was found (P < 0.05). No influence upon the metabolic activity of thrombocytes could be detected.
Neutrophil Functions in Lead-Exposed Workers
Authors: Bergeret A. , pouget E. , Tedone R. , Meygret T. , Cadot R. , Descotes J.
Published: December 2008

Neutrophil functions were studied in 38 lead-exposed workers compared to 34 controls. Both groups were matched according to age, sex, drinking and smoking habits, ethnic origin and drug intake. Blood lead levels were found to be seven times higher in exposed workers than in controls. Phagocytosis assayed by chemiluminescence was found to be slightly but not significantly altered in exposed workers. In contrast, chemotaxis using the agarose technique was significantly depressed. These results are in agreement with previous in-vitro findings. A further assessment of clinical consequences is warranted.
Histochemical Demonstration of Calcium Accumulation in Muscle Fibres after Experimental Organophosphate Poisoning
Authors: Inns R.H. , Tuckwell N.J. , Bright J.E. , Marrs T.C.
Published: December 2008

The LD50 of subcutaneously-injected sarin (GB: isopropyl methylphosphonofluoridate) in mice was 172 μg kg-1. Mice were treated with sarin at doses between 25 and 150 μg kg-1, administered subcutaneously. After sacrifice of the animals, the diaphragms were removed and stained for acetylcholinesterase activity and the presence of ionized calcium. Calcium was found in the diaphragms of those mice to which sarin had been administered at doses of 50 μg kg-1 or above. Calcium accumulation was not present in diaphragms from those animals that had received 25 μg kg-1. Calcium accumulation occurred earliest and remained longest in diaphragms from those animals receiving the highest doses. Accumulation of calcium was associated with end-plates, as demonstrated by an acetylcholinesterase histochemical method.
Management of Methomyl Poisoning
Authors: Martinez-Chuecos J. , Molinero-Somolinos F. , Solé-Violàn J. , Rubio-Sanz R.
Published: December 2008

Eleven patients who suffered methomyl poisoning were admitted to the intensive care unit. All of them showed cholinergic symptoms similar to that produced by organophosphate insecticides but of lesser intensity. Plasma cholinesterase activity was normal in four patients and moderately lower in the remainder (always above 32%). All of the patients showed miosis and none presented with bradycardia. No complications were detected in the acute stage or on further examination a month later.

The treatment applied was: (1) gastric lavage or washing the skin; (2) the administration of activated charcoal; (3) small doses of atropine according to symptoms (average of total dose 4.3 mg). All of the patients recovered within 24-48 h.

In conclusion, we can assume that methomyl poisoning does not produce serious complications if moderate surveillance is assumed. Only small doses of atropine are required to counteract symptoms.
Biological Effects of Inhaled 239PuO2 in Rats with Pre-existing Pulmonary Emphysema
Authors: Lundgren D.L. , Mauderly J.L. , Carlton W.W. , Hahn F.F. , Diel J.H.
Published: December 2008

The modifying effects of pre-existing pulmonary emphysema on the deposition, distribution, retention and effects of inhaled 239PuO2 in the rat were investigated. The presence of emphysema in the rats was documented by morphometric and respiratory function measurements. For rats exposed to similar airborne concentrations of 239PuO2, initial lung burdens of 239Pu per kg body mass were lower in rats with emphysema than in those without emphysema; however, the retention of 239Pu over time was similar in both groups. The distribution of 239Pu particles in the lungs of rats with emphysema tended to be more random than in the lungs of control rats. The life span, and incidences of non-neoplastic and neoplastic lesions in the lung, and risk of lung tumours per unit of alpha dose to the lungs in the rats with emphysema were similar to or less than in the control rats, when groups with similar initial lung burdens of 239Pu were compared. The results of this study suggest that humans with uncomplicated pulmonary emphysema are not necessarily more sensitive to the carcinogenic effects of inhaled 239PuO2 than individuals with normal lungs.
EEG Appearances in Acute Carbamazepine Toxicity
Authors: Howard R.S. , Trend P. StJ. , Townsend H.R.A.
Published: December 2008

A 16-year-old woman deliberately took a large, toxic overdose of carbamazepine and recovered despite a high plasma level. During the acute phase the EEG was dominated by occipital delta activity suggestive of a brainstem disorder. Following 24-h treatment with activated charcoal the plasma carbamazepine was cleared and the EEG returned to normal.
Chronic Occupational Lead Exposure and Testicular Endocrine Function
Authors: McGregor A.J. , Mason H.J.
Published: December 2008

The effects of moderate lead exposure on testicular endocrine function were evaluated in a group of 90 males who were occupationally exposed to inorganic lead. Lead concentrations in blood and bone were measured as indices of short-term and long-term, cumulative exposure, respectively.

The results of this study show that the lead exposure levels encountered in the UK at present may result in a subclinical increase in follicle stimulating hormone (FSH), which is related to blood lead levels. This suggests that lead may be causing some subclinical primary damage to the seminiferous tubules in the testes. However, at blood lead levels of less than 47 μg dl-1this effect on serum FSH is not apparent. There was no significant effect on serum testosterone concentrations or the free testosterone index. The mean luteinizing hormone (LH) level in the exposed group was found to be lower than in the control population. However, there appeared a confoundingly significant positive correlation between serum luteinizing hormone levels and the length of occupational lead exposure within the exposed group.
Study on Kidney Function in Female Workers Exposed to Perchlorethylene
Authors: Vyskočil A. , Emminger S. , Tejral J. , Fiala Z. , Ettlerova E. , Cermanová A.
Published: December 2008

1 Biochemical markers of kidney damage were examined in 16 female workers chronically exposed to tetrachlorethylene (TCE) in five dry-cleaning shops. The results were compared with those obtained in 13 females non-occupationally exposed to organic solvents.

2 The intensity of exposure was monitored by personal environmental monitoring. The time-weighed average exposure to TCE amounted to 157 mg m-3 (range 9-799 mg m-3). A satisfactory agreement was found between the concentration of TCE in ambient air sampled with the charcoal tube method and with a passive dosimeter.

3 The urinary excretion of lysozyme was increased in the exposed group. No difference was found in the urinary excretion of albumin, β2-microglobulin, lactate dehydrogenase, total proteins or glucose. The prevalence of abnormal values of biochemical parameters in the exposed group did not differ from that observed in the control group. No correlation was found between the level of TCE exposure and biochemical parameters.

4 The present study suggests that chronic exposure to TCE does not lead to renal damage.
Acute Poisoning with a Glyphosate-Surfactant Herbicide ('Roundup'): A Review of 93 Cases
Authors: Talbot Alan Ronald , Shiaw Mon-Han , Huang Jinn-Sheng , Yang Shu-Fen , Goo Tein-Shong , Wang Shur-Hueih , Chen Chao-Liang , Sanford Thomas Richard
Published: December 2008

Between 1 January 1980, and 30 September 1989, 93 cases of exposure to herbicides containing glyphosphate and surfactant ('Roundup') were treated at Changhua Christian Hospital. The average amount of the 41% solution of glyphosate herbicide ingested by non-survivors was 184 ± 70 ml (range 85-200 ml), but much larger amounts (500 ml) were reported to have been ingested by some patients and only resulted in mild to moderate symptomatology. Accidental exposure was asymptomatic after dermal contact with spray (six cases), while mild oral discomfort occurred after accidental ingestion (13 cases). Intentional ingestion (80 cases) resulted in erosion of the gastrointestinal tract (66%), seen as sore throat (43%), dysphagia (31%), and gastrointestinal haemorrhage (8%). Other organs were affected less often (non-specific leucocytosis 65%, lung 23%, liver 19%, cardiovascular 18%, kidney 14%, and CNS 12%). There were seven deaths, all of which occurred within hours of ingestion, two before the patient arrived at the hospital. Deaths following ingestion of 'Roundup' alone were due to a syndrome that involved hypotension, unresponsive to intravenous fluids or vasopressor drugs, and sometimes pulmonary oedema, in the presence of normal central venous pressure.
The Efficacy of DTPA Treatment after Deposition of Thorium Nitrate in the Rat Lung
Authors: Stradling G.N. , Moody J.C. , Gray S.A. , Ellender M. , Hodgson A.
Published: December 2008

The efficacy of CaDTPA and ZnDTPA, the chelating agents of choice for several actinide elements, have been evaluated after the deposition of thorium in the rat lung in widely different amounts. The results showed that:

1 When the initial mass concentration of thorium simulated human exposure to four times the annual limits on intake for 232Th, the prompt (300 or 1000 μmol kg -1 body weight at 0.02 d) or repeated (30 or 300 μmol kg-1 body weight at 0.02, 0.25, 1,2,3 d) administration of CaDTPA were at best only moderately successful for enhancing the elimination of thorium. By 7 d after exposure, the body contents of thorium were, respectively, about 74%, 65%, 90% and 74% of those present in untreated animals.

2 When the mass concentration simulated 1.7 X 10-3 times the annual limits on intake for 232Th, the efficacy of treatment was not increased appreciably despite the substantial reduction in mass. After the repeated administration of CaDTPA at doses of 30 and 300 μmol kg-1 using the protocol above, the body contents of thorium by 7 d were, respectively, 69% and 51% of those in untreated animals.

3 Under comparable conditions, the efficacy of ZnDTPA was less than CaDTPA.

The results suggest that more effective chelating agents are needed for the treatment of workers exposed to water soluble thorium compounds.
Life-Threatening Ventricular Arrhythmia (Torsades de Pointes) after Haloperidol Overdose
Authors: Henderson R.A. , Lane S. , Henry J.A.
Published: December 2008

A 48-year-old woman developed QT prolongation and episodes of life-threatening ventricular tachycardia (torsades de pointes) after intentional overdose of haloperidol and orphenadrine. The arrhythmia did not respond to conventional anti-arrhythmic therapy but was suppressed by atrial overdrive pacing. A literature review identified haloperidol as the most likely cause of the torsades de pointes.