bluuebunny/crossref_metadata_2025 huggingface dataset:
Red Cell Haemolysis Induced by SK&F 95018—a Combined Vasodilator and β-Adrenoceptor Antagonist
Authors: Sutton T.J. , Luke J.S.H. , Jones H.B.
Published: December 2008

SK&F 95018, a potential antihypertensive agent with the combined properties of vasodilation and β-adrenoceptor antagonism, induced red urine when given intravenously to a dog. Further studies revealed that in the dog, SK&F 95018 treatment led to haemoglobinaemia, haemoglobinuria and a fall in the red blood cell count. The compound was therefore suspected of causing red cell haemolysis and this was confirmed using dog blood in an in vitro haemolysis test system. Oral administration of the compound to dogs gave no indication of haemolysis, but the animals lost large portions of their dose through vomiting and the lack of effect is therefore questionable. Rats, which have no vomit reflex, were treated orally and although no direct evidence of haemolysis was obtained (e.g. haemoglobinaemia), the presence of polychromasia suggested some loss of mature red blood cells had occurred. Rat blood was haemolysed in vitro by SK&F 95018. Human red cells were also used in the in vitro haemolysis test system and these, too, were lysed by the compound. The haemolysis was shown to be related to the structure of the compound itself rather than to its pharmacological effects and development of SK&F 95018 as an antihypertensive agent was abandoned. Electron microscopy indicated that SK&F 95018 induced alterations in the red cell membrane which led to shape change, characterized by discocyte to spherocyte transformation, and finally haemolysis. The mechanism of this effect remains under investigation.
Poisoning Treatment Centre Admissions Following Acute Incidents Involving Pesticides
Authors: Proudfoot A.T. , Dougall H.
Published: December 2008

1 Adult hospital admissions following acute exposures to pesticides are very uncommon and are more often due to parasuicide than to accidents.

2 Most accidental pesticide incidents are work-related.

3 Males are more likely to be involved than females (2.9:1).

4 Life-threatening and fatal consequences developed in 24% of 54 incidents.

5 Of the 10 fatalities, eight were caused by paraquat, eight were due to parasuicide and two to non-work related accidents.
A Study of the Interaction between Oxytetracycline and Pyridostigmine
Authors: Johnston A. , Hedges A. , Turner P.
Published: December 2008

1 Oxytetracycline and pyridostigmine were given alone and in combination for 4 days to 12 normal male volunteers in a double-blind, randomised cross-over study. On the fifth day, the pharmacokinetic profiles of the two drugs were examined, and blood and plasma cholinesterase activity was measured.

2 No significant interaction on absorption or pharmacokinetics of either drugs was detected when they were given in combination.

3 There was a small but statistically significant increase in erythrocyte cholinesterase when oxytetracycline was given in combination with pyridostigmine, the pharmacological significance of which is not clear.
Influence of Age and Consumption of Tobacco, Alcohol and Caffeine on Antipyrine Clearance
Authors: Loft S. , Døssing M. , Poulsen H.E.
Published: December 2008

1 Antipyrine clearance and average daily consumption of tobacco, alcohol and coffee/tea were determined in 303 healthy men.

2 The antipyrine clearance was positively correlated with the consumption of tobacco (r = 0.24; P < 0.0001) and coffee/tea (r = 0.18; P < 0.001), and negatively with age (r = -0.14; P < 0.05) and the alcohol consumption (r = —0.13; P < 0.05).

3 The multiple regression coefficients suggested an increase in antipyrine clearance of 0.8% per daily cigarette or cup of tea and 1.4% per daily cup of coffee; the decrease per daily drink or year of age was 2.8% or 0.4%, respectively.
Myocardial Failure and Shock in Iron Poisoning
Authors: Tenenbein M. , Kopelow M.L. , deSa D.J.
Published: December 2008

Shock is a well-known complication of iron poisoning. Its aetiology is multifactorial with hypovolaemia due to gastrointestinal blood loss and myocardial depression due to systemic acidosis contributing to its genesis. Primary myocardial dysfunction has not been considered to play a role. Our clinical experiences and autopsy findings in three fatal cases of iron poisoning support myocardial dysfunction and damage as contributing factors to their cardiovascular collapse.

The three patients, all female, were 3½, 16 and 28-years-old. Onset of shock occurred at 1, 2 and 5 days post-ingestion. There was no response to vigorous fluid replacement therapy and aggressive catecholamine infusions. Central venous pressures were elevated. Microscopic examination of postmortem tissue showed myocardial damage and the presence of stainable iron. It is speculated that the myocardial depression is mediated by lipid peroxidation of myocyte organelle membranes due to iron catalysed free radical generation.

The presence of myocardial dysfunction has therapeutic implications. Patients with severe iron poisoning require early and serial measurements of arterial blood pressure, central venous pressure and cardiac output. If primary myocardial dysfunction is documented then fluid replacement, inotropic support and afterload reduction should be considered.
Allopurinol Kinetics after Massive Overdosage
Authors: Ferner R.E. , Simmonds H.A. , Bateman D.N.
Published: December 2008

A 15-year-old girl with normal renal function took 75 tablets of allopurinol 300 mg. She did not suffer any ill-effects. Samples obtained over 84 h showed prolonged elimination of allopurinol, with a half-life of 3.6 h, and oxipurinol, with a half-life of 26 h.
Promutagenic Alkyl Lesions are Induced in the Tissue DNA of Animals Treated with Isoniazid
Authors: Saffhill R. , Fida S. , Bromley M. , O'Connor P.J.
Published: December 2008

Further studies have been carried out to determine mechanisms for the toxic and carcinogenic properties of isoniazid (INH) in laboratory animals.

1 Single doses of INH (1.1 mg per mouse), which if given continuously to Swiss mice result in a 50% incidence of lung tumours, lead to the formation of ∼ 0.5 and∼ 0.3 μmol 06-methylguanine per mol/guanine in the DNA of liver and lung, respectively

2 Repeated doses of INH result in a progressive decrease in the levels of 06-methylguanine in lung DNA and relatively constant levels in hepatic DNA. Treatment with equimolar doses of hydrazine result in higher levels of alkylation in the DNA of liver than of lung.

3 Comparable experiments in Wistar rats show that treatment with hydrazine is very much more effective than INH in inducing the alkylation of liver and lung DNA.

4 Immunocytochemical staining of cryostat sections of liver has been used to show that the formation of 06-methylguanine occurs mainly in the nuclei of hepatocytes.

5 These results demonstrate that treatment with INH leads to the alkylation of tissue DNA and suggest that this may arise via a hydrazine intermediate. The implications of the formation of highly promutagenic lesions in tissue DNA for INH induced toxicity and carcinogenicity are discussed.
Acute Phosphine Poisoning following Ingestion of Aluminium Phosphide
Authors: Misra U.K. , Tripathi A.K. , Pandey R. , Bhargwa B.
Published: December 2008

1 Eight cases of phosphine poisoning following ingestion of aluminium phosphide tablets for suicidal attempt are described. The mean age of the patients was 23 years (range 14-25).

2 The clinical picture consisted of gastritis, altered sensorium and peripheral vascular failure in all cases, cardiac arrhythmia (3), jaundice and renal failure (1 each). Six patients died, the mean hospital stay was 19 h (range 4-72).

3 Post-mortem examination was performed in two patients, revealing pulmonary oedema, gastrointestinal mucosal congestion, petechial haemorrahages on the surface of liver and brain. Histopathological changes included pulmonary oedema, desquamation of the lining epithelium of the bronchioles; vacuolar degeneration of hepatocytes, dilatation and engorgement of hepatic central veins, sinusoids and areas showing nuclear fragmentation.

4 The clinical picture of aluminium phosphide poisoning is described and precaution in the distribution and use of this pesticide recommended.
Myelofibrosis and Focal Segmental Glomerulosclerosis Associated with Toluene Poisoning
Authors: Bosch X. , Campistol J.M. , Montoliu J. , Revert L.
Published: December 2008

A 60-year-old man with long-term exposure to toluene presented with both myelofibrosis and focal segmental glomerulosclerosis. There was also evidence of other toluene-related complications to support the diagnosis of toluene toxicity. The toxic effects of toluene, particularly kidney disorders and haematotoxicity, suggest a relationship between toluene, myelofibrosis and focal segmental glomerulosclerosis.
Acute Organophosphorus Insecticide Poisoning During Pregnancy
Authors: Karalliedde L. , Senanayake N. , Ariaratnam A.
Published: December 2008

Intoxication with organophosphorus insecticides following ingestion with suicidal intent in two patients who were in the second and third trimesters of pregnancy is reported. Successful management of the cholinergic and intermediate phases of poisoning enabled each pregnancy to proceed to term and end in normal vaginal delivery of a healthy baby.
Reproductive Toxicity Tests: Retrospect and Prospect
Authors: Sullivan F.M.
Published: December 2008

1 The design of the classical three segment reproductive test for new drugs is described and the relative merits of the USA/EEC and the Japanese guidelines are discussed.

2 The importance of pharmacokinetic studies in the interpretation of teratology studies and extrapolation to humans is mentioned in relation to caffeine, sodium valproate and cyclophosphamide.

3 Changing ideas on the design of multi-generation studies are reviewed.

4 Recent developments in the fields of behavioural teratology, chemicals in breast milk and transplacental carcinogenesis are described.
Pesticides
Authors: Berry C.L.
Published: December 2008

1 Chemical treatment of crops is essential not only to reduce losses but also to prevent certain food related diseases.

2 Pesticides, unlike many other compounds, are designed to kill higher organisms and thus pose special toxicological problems.

3 It is important to understand the mechanism of action of the pesticide in the target organism in order to assess risk/benefit as accurately as possible.

4 In future the need for pharmacokinetic/dynamic and comparative metabolic data will increase and it will become important to gather human exposure data for certain commonly used compounds, data which are sadly lacking at present.
Ecotoxicology
Authors: Moriarty F.
Published: December 2008

1 Ecotoxicology is concerned ultimately with the effects of pollutants on populations not individuals. Sub-lethal effects, and changes to the environment, can have a greater impact on population size than does acute toxicity.

2 Effective concern about effects of pollutants on wildlife developed after the Second World War with the advent of synthetic pesticides, and the difficulties encountered then in the evaluation of the effects of insecticides are still with us.

3 Effects on wildlife are probably often unnoticed and to demonstrate causes of observed effects usually difficult.

4 Two underlying problems are that ecology is still a relatively young science and that we lack a consensus on the value of wildlife.

5 We need to improve our predictive abilities for effects of pollutants and we also need long-term monitoring schemes that have clear objectives.
Detecting Adverse Reactions to Drugs
Authors: Bennett P.N.
Published: December 2008

1 Present attitudes to drug safety have been shaped largely by a series of disasters.

2 In 1937 about 107 people in the USA died of poisoning by diethylene glycol used as a vehicle for sulphanilamide which led to the requirement that all formulations must be licensed by the FDA before marketing.

3 Up to 1960 the rate of production of new drugs outstripped the ability to introduce them safely. In Germany, thalidomide, an effective sedative, had been introduced in 1956 but it was not until 1961, when an estimated 10 000 babies worldwide had been born with birth deformities, that the teratogenicity of this compound was recognized.

4 Further legislation soon followed, both reducing the number and lengthening the time required to introduce a new drug onto the market. However, problems were encountered with practolol in the 1970s and with benoxaprofen in the 1980s, the latter highlighting the need to make special provision for drug use in the elderly.

5 As to the future, more attention will be paid to the special needs of children and to the possible effects of genetic differences in metabolism.
Clinical and Sub-clinical Lead Poisoning: A Laboratory Perspective
Authors: Braithwaite R.A. , Brown S.S.
Published: December 2008

1 The background, scope and limitations of laboratory methods for the diagnosis of inorganic dead poisoning are outlined in the context of the work of a specialist clinical laboratory for trace element analysis.

2 Data for blood lead, haemoglobin and erythrocyte zinc protoporphyrin concentrations are presented in cases of clinical and sub-clinical poisoning due to accidental or occupational exposure.

3 Data from population surveys of children and adults subject to either environmental or occupational exposure are also shown.

4 In general, analysis for lead in an appropriate specimen of blood offers the single most useful index of exposure.

5 The importance of good accuracy control in such measurements is emphasized.
Factors Influencing the Uptake of Cadmium into Cells in vitro
Authors: Klug S. , Planas-Bohne F. , Taylor D.M.
Published: December 2008

The uptake of cadmium was studied in Chinese Hamster Ovary (CHO) cells. Cadmium accumulates rapidly against a concentration gradient and uptake is dependent on incubation temperature. The presence of serum or albumin results in a reduction in Cd uptake. Several substances known to influence certain metabolic steps of cell metabolism were used to influence Cd accumulation. Of these compounds, those that blocked the SH groups of the plasma membrane exerted the strongest influence. The effect of inhibitors of endocytosis was less pronounced.
A Signal Assay for the Detection of Genotoxic Compounds: Application on the Urines of Cancer Patients on Chemotherapy and of Nurses Handling Cytotoxic Drugs
Authors: Burgaz S. , Özdamar Y.N. , Karakaya A.E.
Published: December 2008

1 The excretion of thioethers was determined in the urine of nurses handling cytotoxic drugs (n = 10) and cancer patients under chemotherapy (n = 32).

2 An occupational non-exposed group served as control ( n = 28).

3 We found no association between the handling of cytotoxic drugs and occupational exposure of nurses. Cancer patients under chemotherapy showed abnormally high values of thioethers, while urinary thioether concentration was, consistently, rather low in some individuals under intensive chemotherapy.

4 We conclude that periodical urinary thioether determinations should be made available to hospital staff as well as cancer patients to minimize the risks of the cytotoxic drugs.
Accidental Feeding of a Dilute Antiseptic Solution (Chlorhexidine 0.05% with Cetrimide 1%) to Five Babies
Authors: Mucklow E.S.
Published: December 2008

Five normal newborn breast fed babies were accidentally fed a dilute antiseptic solution (chlorhexidine 0.05% with cetrimide 1%) in place of sterile water, developing caustic burns of the lips, mouth and tongue within minutes; one baby became quite severely ill due to acute pulmonary oedema, but all survived without sequelae.
A New Method for Predicting the Outcome and Survival Period in Paraquat Poisoning
Authors: Suzuki K. , Takasu N. , Arita S. , Maenosono A. , Ishimatsu S. , Nishina M. , Tanaka S. , Kohama A.
Published: December 2008

1 To elucidate the importance of lung damage in the prognosis of paraquat poisoning, the respiratory index (RI: A-aDO2/PO2) was analysed in 51 patients with paraquat poisoning.

2 Progressive deterioration of the RI was observed in 43 non-survivors, but not in 8 survivors. In addition, the RI of non-survivors became greater than 1.5 in the course of their poisoning, while that of the survivors remained less than 1.5.

3 The level of the RI (i.e. whether it became greater than 1.5 or not) was found to be a good indicator for the prognosis for life.

4 The RI-time, defined as the time taken from ingestion for the RI to be greater than 1.5, was found to be a good indicator for predicting the survival period in fatal cases.

5 As a result, we conclude that it is important and useful to examine a series of RI and the RI-time in poisoned patients not only to provide proper respiratory care, but also to predict outcome and survival period.
Arsenic-induced Skin Toxicity
Authors: Shannon R.L. , Strayer D.S.
Published: December 2008

We reviewed available literature on the effects of inorganic arsenic on the skin to determine the potential hazards and to collate information regarding dosage and exposure to the incidence of skin cancer. Arsenic intake may result from occupational or medicinal exposure, or from drinking well water in areas with high arsenic levels in the soil. Arsenic causes a variety of benign skin lesions including hyperpigmentation and hyperkeratosis. Some hyperkeratotic lesions and squamous cell carcinomas in situ may progress to invasive carcinoma; other invasive squamous cell carcinomas will develop de novo. These cutaneous squamous cancers may metastasize; mortality is low, but has been reported. Locally invasive but non-metastasizing basal cell carcinomas may arise as well. These lesions occur in a characteristic pattern of distribution and are usually multiple. Observers reporting medicinally administered arsenic have described dose-response relationships between the amount of arsenic ingested and the frequency of various skin lesions. For arsenic found in drinking water, however, there is more controversy regarding the doses and exposure times necessary for cutaneous toxicity.
Effect of Homeopathic Dilutions on Subcellular Enzymatic Activity
Authors: Petit C. , Belon P. , Got R.
Published: December 2008

The activity of various inhibitors on several subcellular enzymes was studied. First we determined the inhibitory concentration required to reduce maximum enzymatic activity by 50%, then the effect of various hahnemannian dilutions of the same inhibitory agent was tested. Seven inhibitory agents were tested in this way on seven different enzymatic systems. No effects of these hahnemannian dilutions were shown.
Acute Butylglycol Intoxication: A Case Report
Authors: Gijsenbergh F.P. , Jenco M. , Veulemans H. , Groeseneken D. , Verberckmoes R. , Delooz H.H.
Published: December 2008

A rare case of butylglycol intoxication in a suicide attempt is reported. Coma and hypotension were present on admission and severe metabolic acidosis arose subsequently. Forced diuresis and haemodialysis led to an uneventful outcome.
Acute Resin Phenol-formaldehyde Intoxication. A Life Threatening Occupational Hazard
Authors: Cohen N. , Modai D. , Khahil A. , Golik A.
Published: December 2008

1 A 38-year-old previously healthy worker accidentally spilled phenol-formaldehyde resin over a large area of his skin.

2 Several days later he was hospitalized with extensive necrotic skin lesions, fever, hypertension, adult respiratory distress syndrome (ARDS), proteinuria and renal functional impairment.

3 All symptoms improved progressively and eventually disappeared.

4 We propose that toxic materials originating from the necrotic skin lesions and the continued facilitated absorption of the resin and/or its components via the skin lesions were the main factors responsible for this alarming multisystem involvement.

5 Workers handling this material should be instructed to take appropriate precautions and physicians should be alerted to the potential pathophysiological consequences.
Diagnosis and Treatment of Acute Poisoning with Volatile Substances
Authors: Meredith T.J. , Ruprah M. , Liddle A. , Flanagan R.J.
Published: December 2008

1 The acute toxicity of many volatile compounds is similar, being more related to physical properties than to chemical structure.

2 Volatile substance abusers experiences euphoria and disinhibition but this may be followed by nausea and vomiting, dizziness, coughing and increased salivation; cardiac arrhythmias, convulsions, coma and death occur in severe cases.

3 Laboratory analysis of blood and urine samples collected up to 24 h post-exposure may be helpful if the diagnosis of volatile substance abuse is in doubt.

4 There is only a weak correlation between blood toluene and 1,1,1-trichloroethane concentrations and the clinical features of toxicity, possibly because of rapid initial tissue distribution and elimination.

5 Recovery normally occurs quickly once exposure has ceased but support for respiratory, renal or hepatic failure may be needed as well as treatment for cardiac arrhythmias. Therapy with intravenous acetylcysteine should be considered in cases of acute carbon tetrachloride poisoning.
Chronic Neurological Toxicity Associated with Exposure to Volatile Substances
Authors: Lolin Y.
Published: December 2008

1 The main neurological disorders associated with chronic VSA are peripheral neuropathy, cerebellar disease, chronic encephalopathy and dementia. Apart from peripheral neuropathy, the clinical features are non-specific, evidence for solvent-related toxicity is in most cases circumstantial and there is no clear dose/response relationship.

2 Peripheral neuropathy is mainly associated with n-hexane and methyl n-butyl ketone.

3 Cerebellar disease is usually associated with toluene exposure; in the more severe cases there is often radiological evidence of irreversible cerebellar atrophy.

4 Chronic encephalopathy and dementia are the most serious consequence of solvent exposure, particularly to toluene in abusers and to mixed solvents in industrial workers. Post-mortem studies in some abusers have shown generalized axonal degeneration, demyelination and brain atrophy.

5 Further studies on low level solvent exposure are needed as little is known about the neurological consequences of mild VSA, especially as regards individual susceptibility and possible interactions between solvents and other toxins such as ethanol.
Government, Trade and Industry and Other Preventative Responses to Volatile Substance Abuse
Authors: Liss B.I.
Published: December 2008

1 Since the early 1960s the USA has attempted to combat the problem of volatile substance abuse through legislation including restricting sales, banning 'sniffing', labelling and adding unpleasant smells to abused products. None of this legislation appears to have had the desired effect.

2 VSA has been a growing problem in Britain since the 1970s and presently kills two people per week. The British Government initially adopted a low profile approach, although legislation restricting the sale of abused products was introduced in 1985.

3 In 1984 the British Adhesives Manufacturers Association founded Re-Solv, the society for the prevention of solvent and volatile substance abuse; it is now an independent national charity. Re-solv believe that a broad education programme is needed to combat VSA and are involved in many such projects.
Volatile Substance Abuse within a Health Education Context
Authors: Lee J.T.
Published: December 2008

1 Drug education has to involve exposure not only to knowledge about drug and volatile substance abuse, but also to the effect that attitudes, values, external influences and personal and social skills have on drug behaviour.

2 Such education has also to consider the methods used, the learning process itself, and the need for self-esteem to be enhanced during this process.

3 There is a need to develop personal and social skills which will form the foundation for considering areas such as volatile substance abuse. The school must be supported by the home and by the community.

4 A range of practical resources produced by TACADE (The Advisory Council on Alcohol and Drug Education) allow the translation of this theory of drug education into a practical approach within education.
Chemical Toxicology for the Coroner
Authors: Tormey W.P. , Crosse H. , Pierce A.
Published: December 2008

Toxicology results from all 302 coroners' cases referred to the supraregional unit at Beaumont Hospital over the one year period December 1987 to November 1988 are detailed. Clinical details were provided in 69.5% and formed the basis for the formation of four groups; road traffic accidents, suicides, possible suicides and possible carbon monoxide poisonings. All tests reported were instigated by the referring pathologist on behalf of the coroner. Alcohol was measured in all except 11 patients and a positive result was found in 44%. Drug screens were performed in 68.5% of cases with a positive finding in 30%. At least one positive result was found in 61.9% of the total. In the 60.4% of 53 road accident victims where alcohol was found, the median value was 117 mg/dl. COHb was measured in 23 cases and the median saturation was 45%. There were 12 suicides and agents found included paraquat, CO, cyanide, pancuronium bromide, and amitriptyline. Alcohol levels greater than 120 mg/dl were present in seven. In the 22 cases of suspected suicide, 77.3% were positive for drugs and more than one substance was found in 45.4%.
Oral and Dermal Pharmacokinetics of Triclopyr in Human Volunteers
Authors: Carmichael N.G. , Nolan R.J. , Perkins J.M. , Davies R. , Warrington S.J.
Published: December 2008

Blood levels and urinary excretion of triclopyr, the active ingredient in Garlon® herbicides, were followed in six volunteers given single oral doses of 0.1 and 0.5 mg/kg body weight. Five of these volunteers later received dermal applications of Garlon 4 herbicide formulation equivlant to 3.7 mg triclopyr/kg body weight applied to the forearm. Following oral administration blood levels peaked at 2-3 h and declined to undetectable levels within 48 h; more than 80% of. the dose was found as unchanged triclopyr in the urine. A two-compartment pharmacokinetic model was used to describe the time-course of triclopyr clearance; half-lives for the rapid initial and slower terminal phases were 1.3 h and 5.1 h respectively, and were independent of dose. Due to the slow half-life for dermal absorption (t½ = 16.8 h) the rapid initial elimination phase was obscured and the pharmacokinetics could be simplified by a one-compartment model. An average of 1.37% of the applied dose was recovered in the urine; when corrected for recovery after oral administration this was equivalent to an absorption of 1.65%. Triclopyr is slowly absorbed through skin and is rapidly eliminated. It has very low potential to accumulate in man or to be absorbed through the skin in acutely toxic amounts.
Effect of Subacute Oral Intake of the Food Antioxidant Butylated Hydroxyanisole on Clinical Parameters and Phase-I and -II Biotransformation Capacity in Man
Authors: Verhagen H. , Maas L.M. , Beckers R.H.G. , Thijssen H.H.W. , ten Hoor F. , Henderson P. Th. , Kleinjans J.C.S.
Published: December 2008

A study is presented in which eight healthy male non-smoking volunteers ingested a daily amount of 0.5 mg/kg butylated hydroxyanisole (BHA) for 10 consecutive days. Blood samples were taken on days -6 and 0 before and on days 4 and 7 after the first BHA administration for the assessment of standard clinical plasma parameters (L-aspartate aminotransferase, L-alanine-aminotransferase, L-gamma-glutamyltranspeptidase, creatine phosphokinase, lactate dehydrogenase, total protein, albumin, urea, creatinine, Na+, and Cl-). Antipyrine (500 mg p.o.) and paracetamol (500 mg p.o.) were administered before and during BHA administration as test substances to measure phase-I and phase-11 biotransformation capacity. Saliva samples and urine were subsequently collected for the assessment of kinetic parameters (e.g. saliva elimination half-life, saliva clearance, apparent volume of distribution) and urinary excretion of metabolites. Kinetic plasma parameters of BHA itself were determined in plasma samples obtained via a catheter in an arm vein after oral BHA intake on days 0 and 7. Levels of antipyrine, paracetamol, BHA and metabolites in plasma, saliva or urine were quantified by standard or newly developed reversed-phase high-performance liquid chromatography methods. Urinary excretion of Na+, K +, and Cl-, as well as osmolality of urine were measured on three days before and six days during BHA administration.

Generally, no significant differences were detected in the parameters measured, indicating that oral administration of BHA to men for 10 days remains without effects on clinical biochemical parameters and phase-I and phase-II biotransformation capacity. In contrast, urinary excretion of metabolites of BHA was significantly increased on days 3 and 7 vs. the first day of BHA administration. This may result either from an induction or inhibition of BHA-specific phase-I and -II metabolizing enzymes in man, or from a bioaccumulation of BHA and/or its metabolites in the body.
Total Exclusion from External Respiration Protects Lungs from Development of Fibrosis after Paraquat Intoxication
Authors: Fogt F. , Zilker T.
Published: December 2008

Most survivors of paraquat intoxication go on to develop fibrosis of the lung leading to death within a few weeks. The pathogenic effects of paraquat are based on the formation of oxygen free radicals. A cascade reaction occurs at the cell membrane which is damaged and cell integrity is destroyed. Fibroblasts migrate into the damaged region leading to the laying down of collagen and subsequent fibrosis. Currently paraquat intoxication is treated with gastrointestinal lavage, haemoperfusion and haemodialysis with mixed results. Artificial respiration with low percentage of inspired oxygen is instituted in order to decrease the possible release of oxygen radicals. However, in most cases, developing fibrosis prevents this treatment continuing and requires increased concentrations of inspired O2 and increased ventilation pressure. The combination of increased FiO2 and barotrauma leads to a vicious circle of parenchymal lung damage.

In this study we present a treatment designed to avoid the development of lung fibrosis using total exclusion of segments of the lung from external ventilation.

Exclusion from external ventilation was performed in animal experiments by instillation of Ethibloc, an amino acid glue, in one main bronchus to create an atelectasis. In different experimental groups this procedure was performed before and after intraperitoneal intoxication with paraquat. Four to twelve days later the experimental animals were sacrified and the ventilated lungs and the atelectatic lungs were compared.

The ventilated lungs showed dose-dependent damage to the alveolar epithelium and gross interstitial oedema. In some cases fibrosis was seen. The atelectatic parts of the lung were not different from the control group. In this study we have shown that total exclusion from ventilation prevents the development of lung fibrosis after paraquat intoxication.
Exposure to Paraquat Through Skin Absorption: Clinical and Laboratory Observations of Accidental Splashing on Healthy Skin of Agricultural Workers
Authors: Hoffer E. , Taitelman U.
Published: December 2008

Data concerning 15 consecutive cases of single exposures of the skin or eyes during work to paraquat solutions are presented. Urine and serum were analysed for paraquat in all these cases at the laboratory of the Israel Poison Information Center. From these data it is apparent that a single exposure of healthy skin to paraquat solutions caused only local lesions. No systemic effect was detected in these patients.
The Rarity of Liver Toxicity in Patients Treated with Coumarin (1, 2-Benzopyrone)
Authors: Cox D. , O'Kennedy R. , Thornes R.D.
Published: December 2008

1 Two thousand, one hundred and seventy-three patients with cancer or chronic infections were treated with coumarin in a clinical trial.

2 0.37% of these patients developed elevated liver enzyme levels during therapy with coumarin.

3 This hepatitis was probably a form of idiosyncratic hepatotoxicity and may have been immune in origin.
Self-poisoning in Sri Lanka: Factors Determining the Choice of the Poisoning Agents
Authors: Hettiarachchi J. , Kodithuwakku G.C.S.
Published: December 2008

Sri Lanka is a developing agricultural country with a high fatality rate due to self-poisoning with very toxic agrochemicals as the main poisoning agents. A prospective study of 97 consecutive admissions following self-poisoning reveals that easy availability of the agrochemicals together with the lack of knowledge regarding their lethality were the main causative factors determining the choice of poisoning agents. Developing community awareness of the lethality of these substances, educating the farmers with regards to proper storage and disposal of agrochemicals together with stricter legislation regarding their sale and distribution may reduce the incidence of self-poisoning due to these agents with a consequent reduction in mortality due to self-poisoning.
Effect of Occupational Lead Exposure on Serum 1,25-dihydroxyvitamin D Levels
Authors: Mason H.J. , Somervaille L.J. , Wright A.L. , Chettle D.R. , Scott M.C.
Published: December 2008

The effects of lead exposure on serum 1,25-dihydroxyvitamin D levels and calcium homeostasis have been studied in 63 males occupationally exposed to the metal in the UK. The exposure indices used were blood lead, reflecting short-term exposure, and an in vivo X-ray fluorescence measurement of tibia lead which reflects cumulative lead exposure.

Serum 1,25-dihydroxyvitamin D levels were higher than those in a referent population, who were non-occupationally exposed to lead, and were correlated with both blood lead and tibia lead. Multiple regression analysis suggested that blood lead was the variable responsible for the increase in serum 1,25-dihydroxyvitamin D.

There were no other abnormalities in calcium metabolism associated with the degree of lead exposure.
A Case of Unusual Suicidal Poisoning by the Organophosphorus Insecticide Dimethoate
Authors: Jovanović D. , Randjelović S. , Joksović D.
Published: December 2008

A 20-year-old male who attempted suicide by injecting subcutaneously 10 ml of Sistemin 40 (40% dimethoate) was admitted 16 h later. General weakness, muscular fibrillations and a marked inhibition of red blood cell and serum cholinestrases were the prominent signs of intoxication. The antidotal treatment of intermittent boluses of atropine, oxime HI-6 and diazepam was combined with symptomatic therapy. Cholinesterase activity decreased within the next 3 d. In contrast to the marked general improvement of the patient, the return of cholinesterase activities was very slow. The patient was discharged 24 d after the poisoning with no notable consequences which could be ascribed to the intoxication.
Accidental Poisoning with Podophyllin
Authors: Holdright Diana R. , Jahangiri Marjan
Published: December 2008

Podophyllin is available without prescription and is commonly used in the topical treatment of warts. We describe a case of accidental ingestion of podophyllin, mistaken for cough linctus, and its resultant toxicity.
Bronchial Provocation Testing of Sodium Iso-nonanoyl Oxybenzene Sulphonate
Authors: Ferguson H. , Thomas K.E. , Ollier S. , Davies R.J.
Published: December 2008

1 Asthmatic symptoms have been reported in workers following occupational exposure to certain low molecular ratio chemicals.

2 A small number of workers involved in the initial manufacture of a new low tempeature bleach activating chemical, sodium iso-nonanoyl oxybenzene sulphonate (SINOS) developed rashes, rhinitis and conjunctivitis following exposure to the compound. One worker also developed asthma.

An investigative study was undertaken to examine the possible asthmatic effects of inhaling SINOS in naive non-asthmatic and asthmatic subjects handling the material in the laboratory setting.

3 Since SINOS has a similar chemical structure to aspirin, it was hypothesized that SINOS-associated asthma might be elicited by a mechanism similar to the mechanism associated with aspirin asthma. Therefore aspirin-sensitive asthmatics were also included in the study.

4 No adverse respiratory reactions were observed in the non-asthmatic subjects or in the aspirin and non-aspirin-sensitive patient volunteers following exposure to SINOS dust at atmospheric concentrations of up to 36.3 μg m-3.

5 Skin prick tests to increasing concentrations of SINOS were carried out in all subjects. No positive reactions were observed on any occasion.

6 This study indicates that SINOS does not elicit asthma via a mechanism similar to aspirin. Additionally, the study suggests that the addition of SINOS to washing powder will not cause significant respiratory reactions in consumers even if they are asthmatic or intolerant to aspirin.
Drug Adsorption to Charcoals and Anionic Binding Resins
Authors: Al-Shareef A.H. , Buss D.C. , Routledge P.A.
Published: December 2008

1. The in-vitro binding of four drugs with differing physiochemical properties to two commercial charcoal preparations and two anionic binding resins was studied at 37°C and pH 7.4.

2. The two charcoal preparations (Carbomix and Medicoal) behaved similarly and adsorbed metoclopramide and antipyrine to a greater degree than warfarin or paracetamol.

3. Cholestyramine had a significantly greater maximum adsorption capacity (K2) for warfarin and significantly lower adsorption capacity for paracetamol and metoclopramide than did the charcoals.

4. Colestipol behaved similarly but also bound metoclopramide to a significantly greater extent than did either cholestyramine or charcoal and antipyrine to a significantly lesser extent than did Carbomix.

5. There appeared to be no consistent relationship between the maximum adsorption capacity of the adsorbents for the drugs tested and the physicochemical properties of those drugs (e.g. basic or acidic structure, p Ka or molecular weight).
Use of Glycopyrrolate and Atropine in Acute Organophosphorus Poisoning
Authors: Tracey J.A. , Gallagher H.
Published: December 2008

Two cases of organophosphorus poisoning are reported. Both were treated with a combination of atropine and glycopyrrolate as well as benzodiazepine and pralidoxime. The advantages of glycopyrrolate over atropine are discussed.
Metabolism of Aspirin after Therapeutic and Toxic Doses
Authors: Patel D.K. , Hesse A. , Ogunbona A. , Notarianni L.J. , Bennett P.N.
Published: December 2008

1 The urinary recovery of metabolites of aspirin (ASA) was studied in 45 volunteers who took a therapeutic dose (600 mg) of ASA by mouth and in 37 patients who took ASA in overdose.

2 The main metabolite recovered from the volunteers was the glycine conjugate, salicyluric acid (SUA), which accounted for 75.01 ± 1.19% of total urinary metabolites, whereas salicylic acid (SA) accounted for 8.82 ± 0.56%. Recovery of SUA was negatively correlated with that of SA (r = -0.8625, P < 0.001).

3 In 24 patients with admission plasma salicylate concentrations of 240-360 mg 1-1, SUA accounted for 46.66 ± 3.22% and SA for 31.88 ± 4.02%.

4 In 13 patients with admission plasma salicylate concentrations of 715-870 mg 1-1, SUA accounted for 21.57 ± 3.65% and SA for 64.72 ± 4.82%.

5 Reduced excretion of salicylate as SUA was also accompanied by increased elimination as gentisic acid and salicylic acid phenolic glucuronide indicating that the unsaturated processes that lead to the formation of these metabolites contribute significantly (22-23%) to the inactivation of large doses of salicylate.

6 While the Michalis-Menten kinetics of ASA have been well demonstrated at lower doses, our findings illustrate the progressive saturation of SUA formation under conditions of increasing ASA load to toxic amounts and raise issues about the in-vivo glycine pool when ASA is taken in overdose.
Metronidazole Elimination is Preserved in the Elderly
Authors: Loft Steffen , Egsmose Charlotte , Sonne Jesper , Poulsen Henrik Enghusen , Døssing Martin , Andreasen Per Buch
Published: December 2008

1 The disposition of metronidazole and its major metabolites was compared in 11 subjects aged 86 ± 6 years and 8 aged 30 ± 6 years.

2 The plasma clearance of metronidazole was 1.20 ± 0.53 and 1.25 ± 0.22 ml min-1kg-1, the volume of distribution 0.77 ± 0.27 and 0.77 ± 0.09 1 kg-1and the half-life 7.8 ± 1.9 and 7.2 ± 0.9 h in elderly and young subjects, respectively (P > 0.05).

3 The area under the plasma concentration-time curve of the hydroxy metabolite was 32 ± 14 and 21 ± 3 mM min-1(P < 0.05) whereas its half-life was 21 ± 14 and 12 ± 2 h (P < 0.05) in the elderly and young subjects, respectively.

4 The recovery in the urine of metronidazole and its metabolites was 42 ± 21% and 87 ± 6% of dose in elderly and young subjects, respectively (P < 0.05). With this reservation the only elimination pathways of metronidazole affected by old age were the renal excretion of unchanged compound and the hydroxy metabolite.

5 It is concluded that the ability to eliminate metronidazole is preserved in old age and that age-related dose adjustments are not necessary.
Inhibition of β-glucuronidase in Human Urine by Ascorbic Acid
Authors: Young J.C. , Kenyon E.M. , Calabrese E.J.
Published: December 2008

The effects of oral supplementation of ascorbic acid (1500 mg d-1) on urinary β-glucuronidase (β-G) activity was assessed in a double-blind crossover study design over a 3-week period. The subjects on ascorbic acid treatment displayed a statistically significant (P < 0.05) decrease in β-G with an approximate decrease of 25%.
The Effects of Charcoal and Sorbitol (Alone and in Combination) on Plasma Theophylline Concentrations after a Sustained-Release Formulation
Authors: Al-Shareef A.H. , Buss D.C. , Allen E.M. , Routledge P.A.
Published: December 2008

1 The effects of charcoal and sorbitol, alone and in combination, were investigated in eight healthy female volunteers who received 600 mg slow-release theophylline (two 300 mg capsules) .

2 The area under the plasma concentration time curve to 24 h (AUC0-24) after theophylline alone was significantly greater than after both the charcoal and charcoal plus sorbitol phase.

3 Charcoal and charcoal with sorbitol also significantly reduced the maximum plasma theophylline concentration ( Tmax) and time to maximum concentration ( Cmax).

4 Sorbitol significantly increased Cmax and shortened Tmax.

5 Although sorbitol did not reduce the adsorptive efficacy of charcoal, its use alone may be deleterious in poisoning with sustained-release theophylline products.
Peripheral Zonal Hepatic Necrosis Caused by Accidental Ingestion of Methyl Ethyl Ketone Peroxide
Authors: Karhunen P.J. , Ojanperä I. , Lalu K. , Vuori E.
Published: December 2008

Fatal massive peripheral zonal hepatic necrosis developed in a 47-year-old man who accidentally ingested a solution of methyl ethyl ketone peroxide (MEKP) in dimethyl phtalate. Such solutions contain about 10% active oxygen. The clinical course was characterized by temporary cardiac arrest, abdominal burns, severe metabolic acidosis, rapid hepatic failure, rhabdomyolysis and respiratory insufficiency. A fatal outcome resulted 4 d afterwards from hepatic coma associated with blood coagulation disorders. Microscopical examination revealed massive periportal hepatic necrosis accompanied by atypical pseudoductular proliferation. The proliferating cells were probably of bile duct origin and exhibited atypia and mitoses. The pathogenetic mechanism may involve lipid peroxidation caused by free oxygen radicals derived from MEKP.
Evaluation of the Efficacy of Dimercapto Chelating Agents for the Treatment of Systemic Organic Arsenic Poisoning in Rabbits
Authors: Inns R.H. , Rice P. , Bright J.E. , Marrs T.C.
Published: December 2008

1 The standard drug for the treatment of arsenic poisoning is BAL (dimercaprol). BAL possesses marked side-effects and a low safety ratio, drawbacks which new BAL analogues, DMPS and DMSA, do not possess.

2 The efficacy of three chelating agents, BAL, DMPS and DMSA, has been evaluated as a treatment for systemic organic arsenic poisoning, induced by intravenous dichloro(2-chlorovinyl)arsine (lewisite) administration to rabbits. Equimolar dosing schedules were used based upon realistic doses for the most toxic agent, BAL.

3 It was concluded that all three dimercapto chelating agents provided signficant protection against the lethal systemic effects of lewisite, and, under the test conditions reported here, there was no significant difference between them in therapeutic efficacy.

4 The cause of mortality following intravenous lewisite in treated and untreated rabbits was pulmonary damage.

5 It is considered that DMPS and DMSA are worthy of further study as replacements for BAL in the treatment of systemic poisoning by lewisite.
PCB Reduction and Clinical Improvement by Detoxification: an Unexploited Approach?
Authors: Tretjak Ziga , Shields Megan , Beckmann Shelley L.
Published: December 2008

1. A detoxification trial was administered to a female worker from a capacitor factory who had been exposed to polychlorinated biphenyls (PCBs) and other lipophilic industrial chemicals.

2. The patient presented with severe abdominal complaints, chloracne, liver abnormalities, and a spontaneous nipple discharge of approximately 50 ml d-1.

3. PCB levels were high in adipose tissue (102 mg kg-1), serum, (512 μg 1-1), skin lipids (66.3 mg kg-1), and in the nipple discharge (712 μg I-1).

4. The patient's history, the medical evaluation and prior unsuccessful symptomatic treatments were indicative of consequences elicited by occupational exposure to chemicals.

5. Detoxification treatment reduced the PCB levels in adipose tissue to 37.4 mg kg-1 and in serum to 261 μg 1-1, a 63% and 49% reduction, respectively.

6. The nipple discharge ceased and the symptoms improved.

7. Excretion of intact PCBs in sebum was appreciable before treatment and was enhanced by up to five-fold during detoxification.

8. This therapeutic approach appears promising for cases involving occupational exposure to lipophilic chemicals.
Pharmacokinetics and Toxic Effects of Nifedipine in Massive Overdose
Authors: Ferner R.E. , Monkman S. , Riley J. , Cholerton S. , Idle J.R. , Bateman D.N.
Published: December 2008

A 57-year-old man took 30 × 20 mg nifedipine retarded release tablets. He developed hypotension, tachycardia and flushing, but remained in sinus rhythm. The concentration of nifedipine 10 h after overdose was 604 ?g 1-1, and of the M-I metabolite 110 ?g 1-1. Log concentration time curves were linear from 10-72 h for nifedipine, with a half-life of 7.5 h; and for M-I with a half-life of 8.2 h. On this evidence, oral absorption of nifedipine retarded release is complete by 10 h. There was no evidence of saturation of nifedipine or M-I metabolism, even at concentrations ten times above the therapeutic concentration.
Cytogeneticity of Quinalphos and Methyl Parathion in Human Peripheral Lymphocytes
Authors: Rupa D.S. , Reddy P.P. , Reddi O.S.
Published: December 2008

1 Four different concentrations of quinalphos and methyl parathion were tested on human peripheral lymphocytes over different time periods, for the analysis of chromosomal aberrations and sister chromatid exchanges (SCEs).

2 A significant increase in chromosomal aberrations was observed when cells were treated with quinalphos for 48 and 72 h and a significant increase in SCEs was observed at all the concentrations and over all the time periods.

3 Methyl-parathion did not induce chromosomal aberrations but it did induce SCEs significantly over all time periods.