Botham P A
Acute Toxicity Section, ICI Central Toxicology Laboratory, Macclesfield, Cheshire.
Adverse Drug React Acute Poisoning Rev. 1990 Summer;9(2):91-101.
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.
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具有临床意义的免疫抑制,进而增加感染或患癌风险。此外,对农药过敏反应的发生率总体较低。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,这些实验大多使用了高剂量(坦率地说是有毒剂量)的农药,并且使用体内或体外免疫功能测试来监测免疫抑制情况,而这些测试结果很难从对健康的影响角度进行解读。三丁基氧化锡是一个例外,在大鼠中,它在低于引起一般毒性的剂量下就会导致免疫功能障碍,并损害动物抵抗细菌和寄生虫感染的能力。对接触农药可能引起的免疫毒性进行预测性评估,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。除了预测一些过敏反应(呼吸道过敏和自身免疫)需要开发新的专门方法外,潜在免疫毒性的迹象可以从标准血液学检查以及对脾脏、胸腺、淋巴结和骨髓等淋巴器官和组织的评估中获得。对淋巴系统进行病理和组织病理学检查是全球几乎所有农药亚慢性测试指南的一项强制性要求。将专门的,特别是体外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资源,而且在科学上也是不可接受的;此类测试中变化的意义必须等待对免疫系统储备能力的进一步研究。