Immunotoxicological eects of repeated combined exposure by cypermethrin and the heavy metals lead and cadmium in rats L. InstitoÂris a, *, Olga Siroki a ,U È lku U È ndeger b , I. DeÂsi a , L. Nagymajtenyi a a Department of Public Health and WHO Collaborative Centre for Chemical Safety, Szent-Gyo Èrgyi Albert Medical University, Szeged, H-6720 Szeged, Do Âm teÂr 10, Hungary b Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, 06100 Samanpazari, Turkey Received 10 December 1998; accepted 19 July 1999 Abstract The immunotoxic eect of a 28 days oral exposure by 55.4, 22.2, and 11.1 mg/kg cypermethrin (CY) was investigated in 4 weeks old male Wistar rats. The applied test system involved the determination of general toxicological parameters (body weight gain, organ weight of thymus, heart, lung, liver, spleen, kidneys, adrenals and the popliteal lymph node), haematological parameters (white blood cell count, red blood cell count, haematocrit, mean cell volume of red blood cells, cellularity of the femoral bone marrow), as well as immune function assays (splenic plaque forming cell assay, delayed type hypersensitivity reaction). The highest dose resulted in a signi®cant increase of the relative liver weight, and all three doses resulted in (although inconsistent) changes in the haematocrit and MCV values. The maximum of DTH reaction decreased at all three doses. On combination of the highest CY dose with non-eective doses of lead or cadmium the immunotoxic eects of the former were modi®ed. When immunotoxic doses of Cd or Pb were combined with the lowest CY dose, further interactions were observed on the examined parameters. The alterations of the immunotoxic eects of CY by simultaneous exposure with Cd or Pb, as described here, can lead to unexpected health consequences and/or can lead to false positive or negative results in human epidemiological studies. # 1999 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved. Keywords: Immunotoxicity; Lead; Cadmium; Cypermethrin; Rats International Journal of Immunopharmacology 21 (1999) 735±743 0192-0561/99/$20.00 # 1999 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved. PII: S0192-0561(99)00049-1 www.elsevier.com/locate/ijimmpharm * Corresponding author. Tel.: +36-62-455-119; fax: +36-62-455-120. E-mail address: ist@puhe.szote.u-szeged.hu (L. InstitoÂris)