Neishabouri E Zabihi, Hassan Z M, Azizi E, Ostad S N
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Toxicology. 2004 Mar 15;196(3):173-9. doi: 10.1016/j.tox.2003.08.012.
Diazinon (DZN), an organophosphate insecticide, has been used in agriculture for several years. It is possible the residue of this compound to be recycled in the biological system. There is no report on DZN immunotoxicity potential. In the present study, we examined the immunotoxic effects of intraperitoneally administered DZN in the C57bl/6 female mice. Diazinon was administered at doses of 25, 2, and 0.2 mg/kg for 28 days (five injections per week). Animals were then sacrificed to observe the cellularity or histopathological changes in thymus, spleen, bone marrow, and peripheral blood. Furthermore, humoral and cellular functional responses such as Hemagglutination titration (HA), IgM-Plaque Forming Colony Assay (PFC), Delayed-Type-Hypersensitivity (DTH) to SRBC, and T cell subtyping (CD4/CD8) were determined. The results showed that DZN at 25 mg/kg not only could produce gross histopathological changes in thymus and spleen but also could suppress both humoral and cellular activity of the immune system. At lower doses (0.2 and 2 mg/kg) there were no observable alteration in cellularity or histology of immune tissues. However, DZN at medium dose (2 mg/kg per day) could inhibit RBC-cholinesterase and showed a mild decrease (P < 0.1) in thymus/body-weight ratio and DTH response. At dose of 0.2 mg/kg no histopathological or functional disturbances were detectable. These results indicate that DZN has immunosuppressive effects in the C57bl/6 mice at doses more than 2 mg/kg. The present results however indicate that under recommended Allowed Daily Intake (ADI) limit (<0.02 mg/kg), no observable immunotoxicity effect is expected.
二嗪农(DZN)是一种有机磷酸酯类杀虫剂,已在农业中使用多年。这种化合物的残留物有可能在生物系统中循环利用。目前尚无关于二嗪农免疫毒性潜力的报道。在本研究中,我们检测了腹腔注射二嗪农对C57bl/6雌性小鼠的免疫毒性作用。以25、2和0.2mg/kg的剂量给予二嗪农,持续28天(每周注射五次)。然后处死动物,观察胸腺、脾脏、骨髓和外周血中的细胞数量或组织病理学变化。此外,还测定了体液和细胞功能反应,如血凝滴定(HA)、IgM-空斑形成集落测定(PFC)、对SRBC的迟发型超敏反应(DTH)和T细胞亚群分型(CD4/CD8)。结果表明,25mg/kg的二嗪农不仅会在胸腺和脾脏中产生明显的组织病理学变化,还会抑制免疫系统的体液和细胞活性。在较低剂量(0.2和2mg/kg)下,免疫组织的细胞数量或组织学没有明显变化。然而,中等剂量(每天2mg/kg)的二嗪农可抑制红细胞胆碱酯酶,并使胸腺/体重比和DTH反应轻度降低(P<0.1)。在0.2mg/kg的剂量下,未检测到组织病理学或功能紊乱。这些结果表明,二嗪农在剂量超过2mg/kg时对C57bl/6小鼠具有免疫抑制作用。然而,目前的结果表明,在推荐的每日允许摄入量(ADI)限值(<0.02mg/kg)以下,预计不会观察到免疫毒性作用。