Adverse drug reactions and acute poisoning reviews最新文献

Pesticides are currently perceived by the public as posing a major long-term threat to the health of the population. While the acute toxic effects of accidental or intentional ingestion of large doses are accepted, very little is known about the health risks associated with chronic occupational exposure or a life-long intake in food and drinking water. As in most cases of risk assessment, it is the relative risks that must be considered. Pesticides have made a vital contribution to the quality and quantity of food and overall to health both in developed and, most significantly, developing countries, so that their sudden withdrawal would present far more serious health problems than do their potential long-term toxic effects. Genetic engineering may develop seeds that are naturally resistant to many plant diseases, and biological methods of insect control are likely to be used more frequently, but the continued use of pesticides will be necessary for many more years. There is a pressing need for research into the chronic health effects in man of low-level exposure to pesticides, the mechanisms of the toxic effects, and the development of reliable methods for monitoring exposure. The responsibility for ensuring that this work is undertaken must be accepted by governments.

So far there is little evidence that occupational or environmental exposure to pesticides has led to clinically significant immunosuppression, and hence to an increased risk of developing infection or cancer. In addition, the incidence of hypersensitivity reactions to pesticides is generally low. Experiments have been conducted in experimental models that indicate that certain pesticides are immunosuppressive to animals. The majority of these experiments, however, have used high (frankly toxic) doses of pesticides and immunosuppression has been monitored using in vivo or in vitro immune function tests, the results of which are difficult to interpret in terms of effects on health. One exception is tributyltin oxide which, in the rat, causes immune dysfunction at doses below those that cause general toxicity, and which compromises the ability of the animals to resist bacterial and parasitic infection. Predictive assessment of possible immunotoxicity induced by exposure to a pesticide should be structured within the current framework of acute, subacute and chronic testing procedures used for regulatory purposes. With the exception of predicting some hypersensitivity reactions (respiratory allergy and autoimmunity), which would require the development of novel specialized methods, indications of potential immunotoxicity can be obtained from standard haematological investigations and by evaluation of lymphoid organs and tissues such as the spleen, thymus, lymph nodes, and bone marrow. Pathological and histopathological examination of the lymphoid system is a mandatory requirement of nearly all subchronic testing guidelines for pesticides worldwide. The incorporation of specialized, and in particular in vitro, immune function tests into the routine toxicological assessment of a pesticide is not only time-consuming and potentially wasteful of animals, but is also scientifically unacceptable; the significance of changes in such tests must await further research on the reserve capacity of the immune system.

Used alone, the most recently developed cephalosporins are remarkable for their effectiveness and safety. They have a low incidence of relevant nephrotoxicity. All cephalosporins are thought to be potentially nephrotoxic at high doses, and the usual site of damage is the renal tubule. Interstitial nephritis would appear to be much less common. The pathogenesis of nephrotoxicity is therefore thought to be directly dose-related rather than due to hypersensitivity. It is prudent that this be considered when new cephalosporins are evaluated and when the clinician prescribes a cephalosporin, especially when renal function is already compromised.