Human toxicology最新文献

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.

1 PCDDs and PCDFs are ubiquitous and persistent in the environment. They are to be found in body tissues of both humans and animals. 2 The most extensively studied PCDD is 2,3,7,8-TCDD. It has been shown to produce a wide range of effects and is considered to be a (non-genotoxic) carcinogen in animals. 3 Studies into the mechanisms of toxicity so far reveal that there is involvement of a specific receptor (Ah), however further work is required to elucidate the mechanisms of the various effects. 4 Reports on a number of human exposures to PCDDs and PCDFs are described. Results from human epidemiological studies are difficult to interpret: there have been problems in methodology; there has been inadequate information on intake, and exposures have often been to mixtures of PCDDs and/or PCDFs together with other related compounds. 5 Many regulatory authorities faced with the problem of providing an index of risk from exposure to mixtures of PCDDs and PCDFs have employed the concept of 'TCDD equivalents'. 6 Whether or not PCDDs and PCDFs pose a significant human health risk at current levels of exposure they remain of considerable interest to the toxicologist.

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 less than 0.01) in Cpmax, and 25% (P less than 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.

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.

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 microgram/100 ml (9-10%) for adults in both 'exposed' and 'control' groups; about 2 micrograms/100 ml (18%) in traffic police; and about 1.5 micrograms/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.

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.

Lung dissolution of industrial uranium tetrafluoride (UF4) was tested in rats and baboons by intratracheal instillation and inhalation, to check the W classification given to UF4 by the International Commission on Radiological Protection. Rats and baboons were given 10 and 160 micrograms of UF4 per animal respectively. Lung clearance, urinary excretion and tissue distribution of uranium were measured in rats, and urinary excretion was measured in baboons. After intratracheal instillation, daily urinary excretion was fast in both species; 4.8 +/- 0.7 X 10(-2) of the initial lung burden (ILB) in rats and 2.9 +/- 0.3 X 10(-2) in baboons. After inhalation of dry UF4 powder, daily urinary excretion was 5.6 +/- 2.2 X 10(-2) of the ILB in rats and the lung clearance half-life was 7.3 d. The amounts of uranium excreted by rats and baboons were compared to the amounts dissolved in vitro by alveolar macrophages from both species, and also to the amount dissolved chemically by a serum simulant. Both rat and baboon macrophages were clearly shown to be involved in the mechanism of uranium dissolution, since on the first day of macrophage culture, they dissolved 20 and 40% respectively of the amounts of UF4 added to the macrophage cultures, again illustrating the fast dissolution of UF4.(ABSTRACT TRUNCATED AT 250 WORDS)