Ladics G S, Smith C, Heaps K, Loveless S E
Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Co., Newark, Delaware 19714.
J Toxicol Environ Health. 1994 Jun;42(2):143-56. doi: 10.1080/15287399409531869.
The objective of this study was to examine the immunotoxicological effects of the methyl-carbamate pesticide carbaryl via the oral, dermal, or inhalation routes. Male CD rats were exposed to carbaryl 5 d/wk for a 2-wk period. During nose-only inhalation exposures, rats received either 36, 137, or 335 mg/m3 carbaryl in acetone for 6 h. Air only and acetone/air controls were run concurrently. Orally exposed animals received either 1 ml corn oil or 10, 25, or 50 mg/kg carbaryl, while dermally exposed animals received either 2 ml acetone or 100, 500, or 1000 mg/kg carbaryl on their dorsal flank for 6 h. Four days prior to sacrifice, animals from all exposure groups were injected iv with 2 x 10(8) sheep red blood cells (SRBC). The primary immunoglobulin M (IgM) humoral immune response to SRBC was then assessed by measuring SRBC-specific antibody-forming cells (AFC) and levels of serum anti-SRBC IgM antibody, respectively, using the hemolytic plaque assay and an enzyme-linked immunosorbent assay. Individual body weights, spleen, thymus, and liver weights, spleen cell number, and red and white blood cell (RBC, WBC) counts were obtained for each animal. Following nose-only inhalation exposures, dose-dependent decreases in thymus weights, spleen cell number, AFC/spleen, AFC/10(6) splenocytes, and serum levels of SRBC-specific IgM antibody were observed. Significant decreases of 33, 57, and 22% in spleen cell number, AFC/spleen, and thymus weight, respectively, were found at the 335 mg/m3 exposure level. Animals exposed orally to 25 mg/kg carbaryl had a 34% decrease in WBC counts. A 34% decrease in WBC and a 13% increase in RBC counts were observed at the 50 mg/kg oral dose. Significant decreases in liver weights ranging from 11 to 13% were found at all oral exposure levels. Dermal exposure to carbaryl revealed no significant toxicological effects. Results indicate that humoral immune suppression was observed following inhalation, but not following oral or dermal exposures to carbaryl. Immunotoxicological studies evaluating pesticides need to consider relevant exposure routes and dosages for appropriate risk assessment procedures and exposure limits to be established.
本研究的目的是通过口服、皮肤或吸入途径,研究氨基甲酸甲酯类农药西维因的免疫毒理学效应。雄性CD大鼠每周暴露于西维因5天,持续2周。在仅经鼻吸入暴露期间,大鼠接受丙酮中36、137或335 mg/m³的西维因,暴露6小时。同时设置仅空气对照组和丙酮/空气对照组。经口暴露的动物接受1 ml玉米油或10、25或50 mg/kg的西维因,而经皮暴露的动物在其背部侧翼接受2 ml丙酮或100、500或1000 mg/kg的西维因,暴露6小时。在处死前4天,给所有暴露组的动物静脉注射2×10⁸个绵羊红细胞(SRBC)。然后分别使用溶血空斑试验和酶联免疫吸附试验,通过测量SRBC特异性抗体形成细胞(AFC)和血清抗SRBC IgM抗体水平,评估对SRBC的主要免疫球蛋白M(IgM)体液免疫反应。记录每只动物的个体体重、脾脏、胸腺和肝脏重量、脾细胞数量以及红细胞和白细胞(RBC、WBC)计数。在仅经鼻吸入暴露后,观察到胸腺重量、脾细胞数量、AFC/脾脏、AFC/10⁶脾细胞以及血清SRBC特异性IgM抗体水平呈剂量依赖性下降。在335 mg/m³暴露水平下,脾细胞数量、AFC/脾脏和胸腺重量分别显著下降33%、57%和22%。经口暴露于25 mg/kg西维因的动物白细胞计数下降了34%。在经口剂量为50 mg/kg时,观察到白细胞计数下降34%,红细胞计数增加13%。在所有经口暴露水平下,肝脏重量均显著下降11%至13%。经皮暴露于西维因未显示出明显的毒理学效应。结果表明,吸入西维因后观察到体液免疫抑制,但经口或经皮暴露于西维因后未观察到。评估农药的免疫毒理学研究需要考虑相关的暴露途径和剂量,以建立适当的风险评估程序和暴露限值。