Subacute toxicity of orally applied alpha-cypermethrin in Swiss mice.
More details
Hide details
Department of Pathomorphology, Institute of Agricultural Medicine, Lublin, Poland
Ann Agric Environ Med. 2000;7(1):33–41
The effect of a synthetic pyrethroid - alpha-cypermethrin administered per os for 28 days to Swiss mice was examined on phagocytic and bactericidal activity of neutrophils, and leukocytic image, IL-12 p70 level in blood plasma, as well as histologic and ultrastructural picture of the liver, heart, kidneys, lung and spleen. A synthetic pyrethroid alpha-cypermethrin, [(R,S)-alpha-cyano-3-phenoxybenzyl (R,S)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate], produced by the Chemical Plant in Jaworzno was used in the study. The preparation for the application per os was used in doses 1/2 LD50 (25 mg/kg body mass) and 1/5 LD50 (10 mg/kg body mass). The results were presented as mean (x) +/- standard error (SEM) and subjected to statistical analysis by the parametric t-Student test. Subacute poisoning of mice with alpha-cypermethrin in doses 1/2 LD50 and 1/5 LD50 resulted in decreased bactericidal activity of neutrophils. The dose 10 mg/kg body mass had a stronger stimulatory effect on phagocytic activity than 25 mg/kg body mass. Significantly higher numbers of monocytes and lymphocytes were observed in the blood of male mice poisoned with 1/5 LD50 alpha-cypermethrin. The administration of alpha-cypermethrin resulted for both doses in the decrease in IL-12 p70 serum secretion. The lowest IL-12 p70 level (pg/ml) was noted among female mice administered 1/2 LD50 of the preparation. The results of the study may indicate that the pyrethroid in the study had a suppressive effect on Il-12 p70 production. In mice administered 1/5 LD50 or 1/2 LD50 of the preparation examined, histopathologic and ultrastructural changes were observed in the liver and kidneys.
Abbas AK, Murphy KM, Sher A: Functional diversity of helper T lymphocytes. Nature 1996, 383, 787-793.
Cassatella MA, Meda L, Gasperini S, D’Andrea A, Ma-X, Trinchieri G: Interleukin-12 production by human polymorphonuclear leukocytes. Eur J Immunol 1995, 25, 1-5.
Chehimi J, Trincheri G: Interleukin - 12 a bridge between innate resistance and adaptive immunity with a role in infection and acquired immunodeficiency. J Clin Immunol 1994, 14, 149-161.
Chizzonite R, Truitt T, Desai BB, Nunes P, Podlaski FJ, Stern AS, Gately MK: IL-12 receptor. Characterization of the receptor on phytohemagglutinin-activated human lymphoblasts. J Immunol 1992, 148, 3117-3124.
Coffman RL, von der Weid T: Multiple pathways for the initiation of T helper 2 (Th2) responses. J Exp Med 1997, 185, 373-375.
D’Andrea A, Rengaraju M, Valiante NM: Production of natural killer cell stimulatory factor (interleukin - 12) by peripheral blood mononuclear cells. J Exp Med 1992, 176, 1387-1398.
Desai BB, Quinn PM, Wolitzky AG, Mongini PK, Chizzonite R, Gately MK: IL-12. Distribution and regulation of receptor expression. J Immunol 1992, 148, 3125-3132.
Desi I, Varga L, Dobronyi I, Szklenarik G: Immunotoxicological investigation of the effect of a pesticide; cypermethrin. Archiv Toxicol 1985, 8, 305-309.
Desi I, Dobronyi I, Varga L: Immuno-, neuro- and general toxicologic animals studies on a synthetic pyrethroid. Ecotoxicol Environ Safety 1986, 12, 220-232.
Endogen, Inc. Endogen Mouse Interleukin-12 (p70) Elisa, 8 Gill Street Woburn, MA 01801-1721 USA.
Germann T, Guckes S, Bongartz M: Administration of IL-12 during ongoing immune responses fails to permanently suppress and can even enhance the synthesis of antigen-specific IgE. Int Immunol 1995, 7, 1649-1657.
Gillesen S, Carvajal D, Ling P, Podlaski FJ, Stremlo DL, Familletti PC, Gubler U, Presky DH, Stern AS, Gately MK: Mouse interleukin-12 (IL-12) p40 homodimer a potent IL-12 antagonist. Eur J Immunol 1995, 25, 200-206.
Hoellinger H, Lecorsier A, Sonnier M, Leger C, Do-Cao-Tang, Nguyen-Hoang-Nam: Cytotoxicity, cytogenotoxicity and allergenicity tests on certain pyrethroids. Drug Chem Toxicol 1987, 10, 291-310.
Kang K, Kubin M, Cooper KD, Lessin SR, Trinchieri G, Rook AH: IL-12 synthesis by human Langerhans cells. J Immunol 1996, 156, 1442-1447.
Kobayashi M, Fitz L, Ryan M: Identification and purification of natural killer cell stimulatory factor (NKSF) a cytokine with multiple biologic effects on human lumphocytes. J Exp Med 1989, 170, 827-845.
Królikowska-Prasał I, Hifer-Wysocka E, Matysiak W, Romanowska-Sarlej J: Morphologische Beurteilung und Analyse von Superelementen in der Leber von Ratten, die mit Kraftwerk-Aschen enthaltendem Futter gefuttert wurden. Gengenbaurs Morphol Jahrb Leipzig 1990, 136, 565-576.
Kubin M, Kamoun M, Trinchiert G: Interleukin-12 synergizes with B7/CD28 interaction in inducing efficient proliferation and cytokine production by human T cells. J Exp Med. 1994, 180, 211-222.
Kuge S, Watanabe K: Interleukin-12 augments the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes from tumor- infiltrating lymphocytes. Jpn J Cancer Res 1995, 86, 135-139.
Luty S, Maj A: Wpływ alfacypermetryny na poziom wybranych cytokin osoczowych u myszy: IX Zjazd Polskiego Towarzystwa Immunologii Doswiadczalnej i Hlinicznej Warszawa, 16-18.09.1998. Materiały zjazdowe, SGGW, Warszawa, 1998, p. 304.
Luty S, Latuszynska J, Halliop J, Tochman A, Obuchowska D, Przylepa E, Korczak E: Toxicity of dermally applied alpha-cypermethrin in rats. Ann Agric Environ Med. 1998, 5, 109-115.
Luty S, Latuszynska J, Przylepa E: Immunotoksycznoss parakwatu, dichlorfosu i alfacypermetryny wchłanianych przez skóre. Brom Chem Toksykol 1998, 3, 259-263.
Łukowicz-Ratajczak J, Hrechniak J: Wpływ dekametryny na układ immunologiczny. Cz. I. Działanie immunosupresyjne. Bromat Chem Toksykol 1991, 1, 57-61.
Łukowicz-Ratajczak J, Krechniak J, Englot B: Wpływ deltametryny na układ immunologiczny. Cz. II. Wpływ na odpowiedz humoralna i komórkowa. Bromat Chem Toksykol 1992, 3, 263-266.
Macetonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA, Wysocka M, Trinchieri G, Murphy KM, O’Garra A: Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol 1995, 154, 5071-5079.
Madsen C, Cleasson MH, Ropke C: Immunotoxicity of the pyrethroid insecticides delthamethrin and alpha-cypermethrin. Toxicology 1996, 3, 219-227.
MC Daniel KL, Moser VC: Utility of a neurobehavioral screening battery for differentiating the effects of two pyrethroids, permethrin and cypermethrin. Neurotoxicol Teratol 1993, 15, 71-83.
Ministerstwo Zdrowia i Opieki Społecznej: Hryteria Zdrowotne Srodowiska. Tom 82, Cypermetryna. Instytut Medycyny Pracy, Łódz 1995, 15-17.
Nabioullin R, Sone S: Induction mechanism of human blood CD8+ T cell proliferation and cytotoxicity by natural killer cell stimulatory factor (Interleukin-12). Jpn J Cancer Res 1994, 85, 853-861.
Oshima Y, Delaspesse G: T cell derived IL-4 and dendritic cell - derived IL-12 regulate the lymphokine - producing phenotype of alloantigen - primed naive human CD4 T cells. J Immunol 1997, 158, 629-636.
Park BH, Fikrig SM, Smithwick EM: Infection and nitroblue - tetrazolium reduction by neutrophils. Lancet 1968, 2, 532.
Robertson MJ, Soiffer RJ: Response of human natural killer (NK) cells to NK stimulatory factor (NKSF) cytolytic activity and proliferation of NK cells are differentially regulated by NKSF. J Exp Med 1992, 175, 779-788.
Santoni G, Cantalamassa F, Cavanga R, Spreghini E, Piccoli M: Cypermethrin - induced alternation of thymocyte distribution and functions in prenatally - exposed rats. Toxicology 1998, 125, 67-68.
Seder RA, Paul WE: Acquisition of lymphokine producing phenotype by CD4+ T cells. Annu Rev Immunol 1994, 12, 635-673.
Snijders A, Hilkens CM, van der Pouw-Kraan TC, Engel M, Aarden LA, Kapsenberg ML: Regulation of bioactive IL-12 production in lipopolysaccharide-stimulated human monocytes is determined by the expression of the p35 subunit. J Immunol 1996, 156, 1207-1212.
Stern AS, Podlaski FJ, Hulmes JD: Purification to homogenity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc Natl Acad Sci USA 1990, 87, 6808-6812.
Slopek S: Immunology in Practice. PZWL, Warsaw 1979 (In Polish).
Tos-Luty S, Latuszynska J, Przylepa E: Zastosowanie testów płatkowych i odpowiedzi układu granulocytarnego w ocenie narazenia na pestycydy. 16/98/ SPR-1 manuskrypt, Lublin 1999.
Trinchieri G, Wysocka M, D’Andrea A, Rengaraju M, Aste- Amezaga M, Kubin M, Valiante NM, Chehimi J: Natural killer cell stimulatory factor (NKSF) or interleukin-12 is a key regulator of immune respoinse and inflammation. Prog Growth Factor Res 1992, 4, 355-368.
Tulinska J, Kubora J, Janota S, Nyulossy S: Investigation of immunotoxicity of supercypermethrin forte in the Wistar rat. Hum Exp Toxicol 1995, 5, 399-403.
Turka LA, Goodman RE, Rutkowski JL, Sima AA, Merry A, Mitra RS, Wrone-Smith T, Toews G, Strieter RM, Nickoloff BJ: Interleukin-12 a potential link between nerve cells and immune response in inflammatory disorders. Mol Med 1995, 1, 690-699.
Verschoyle RD, Aldrige WN: Structure-activity relationship of some pyrethroids in rats. Arch Toxicol 1980, 45, 325-329.
Vogel LA, Showe LC, Lester TL: Direct binding of IL-12 to humans and murine B lymphocytes. Int Immunol 1996, 8, 1955-1962.