title: Immunotoxicity assessment of sub-chronic oral administration of acetamiprid in Wistar rats.
abstract: BACKGROUND
  Neonicotinoid insecticides are synthetic analogues of nicotine that acts on the central nervous system of insects by blocking post synaptic acetylcholine receptor. Acetamiprid is one of the widely used neonicotinoid class of insecticide used to control sucking insects like aphids, bees, mosquitoes, on crops. Data on the possible immunotoxic nature of acetamiprid are lacking.
  
  
  OBJECTIVE
  The present study was conducted in Wistar rats with the objective of evaluating the immunotoxic potential of acetamiprid administered orally at the dose levels of 27.5, 55 and 110 mg/kg b.w. (equivalent to 5.5, 11 and 22 mg/kg b.w.) for a period of 90 days.
  
  
  METHODS
  In experiment 1, general toxicity testing including the evaluation of clinical signs, hemato-biochemical changes, response of the lymphocytes towards T and B cell mitogens, macrophage function, gross and histopathology of the lymphoid organs (spleen, thymus, lymph nodes, etc.) were performed. In the second experiment, humoral and cell-mediated responses during immunological challenges were evaluated.
  
  
  RESULTS
  Significant decreases were observed in the stimulation index of lymphocyte proliferation to B cell mitogen and in the nitrite production of macrophages of rats treated with 110 mg/kg of acetamiprid. Significant decrease in the lymphoproliferative response towards the B cell mitogen indicated the inability of the B lymphocytes to respond on stimulation that might increase the chances of susceptibility to infections. Acetamiprid also caused 15-28% reduction in nitrite production, an important signal for efficient inflammatory response of macrophages. The functional impairment of macrophages may involve aberrations in the enzymatic degradation of microbes, oxidative burst, generation of free radicals, phagocytosis, release of proinflammatory cytokines and thereby, may hamper host defence causing susceptibility to diseases. No significant changes over hematology, biochemistry, organ weights, histopathology of major immune organs, delayed type hypersensitivity test, response to sRBCs and lymphoproliferation assay for T cell mitogen were observed.
  
  
  CONCLUSIONS
  In conclusion, the results demonstrate for the first time that the subchronic administration of acetamiprid (20% SP-soluble powder) cause significant decreases in the lymphocyte proliferation as well as the macrophage function at the dose level of 110 mg/kg. Considering the chronic population adjusted dose (0.023 mg/kg/day) through dietary exposure for acetamiprid, judicious use of acetamiprid is highly essential. Indiscriminate use of acetamiprid exceeding the doses advised might pose a hazard.
authors.affiliation: Central Animal Facility, SASTRA University , Thanjavur, Tamil Nadu , India.
authors.forename: R K
authors.initials: RK
authors.lastname: Shakthi Devan
authors.forename: P C
authors.initials: PC
authors.lastname: Prabu
authors.forename: S
authors.initials: S
authors.lastname: Panchapakesan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006384:Hemagglutination / Q000187:drug effects; D006386:Hemagglutination Tests; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D000073943:Neonicotinoids; D011725:Pyridines / Q000008:administration & dosage / Q000633:toxicity*; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D059550:Toxicity Tests, Subchronic
chemical_list: D007306:Insecticides; D000073943:Neonicotinoids; D011725:Pyridines; C464485:acetamiprid
keywords: Cell-mediated immunity; humoral immunity; immunotoxicity; neonicotinoids; rats; safety assessment