Are pesticides immunotoxic?

P A Botham
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Abstract

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.

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农药有免疫毒性吗?
到目前为止,几乎没有证据表明职业性或环境性接触农药会导致临床上显著的免疫抑制,从而增加患感染或癌症的风险。此外,农药过敏反应的发生率普遍较低。在实验模型中进行的实验表明,某些农药对动物具有免疫抑制作用。然而,这些实验中的大多数都使用了高剂量(坦率地说是有毒的)杀虫剂,并且通过体内或体外免疫功能测试来监测免疫抑制,其结果很难从对健康的影响方面加以解释。一个例外是氧化三丁基锡,在大鼠中,它在低于一般毒性的剂量下会引起免疫功能障碍,并损害动物抵抗细菌和寄生虫感染的能力。对农药暴露可能引起的免疫毒性的预测性评估应在目前用于监管目的的急性、亚急性和慢性测试程序框架内进行。除了预测一些超敏反应(呼吸道过敏和自身免疫)(这需要开发新的专门方法),潜在免疫毒性的适应症可以从标准血液学调查和淋巴器官和组织(如脾脏、胸腺、淋巴结和骨髓)的评估中获得。淋巴系统的病理和组织病理学检查是全世界几乎所有农药亚慢性测试指南的强制性要求。将专门的、特别是体外的免疫功能测试纳入农药的常规毒理学评估,不仅耗时且可能浪费动物,而且在科学上也是不可接受的;这些测试变化的意义必须等待对免疫系统储备能力的进一步研究。
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