Immunotoxicological Investigation of Combined Subacute Propoxur and Heavy Metal (Cd, Pb) Exposure in Rats

László Institóris, Olga Siroki and László Nagymajtényi

Department of Public Health, Faculty of General Medicine, University of Szeged, Hungary

Corresponding author: László Institóris
    Department of Public Health, Faculty of Medicine,
    A. Szent-Györgyi Medical and Pharmaceutical Center
    University of Szeged, Dóm tér 10.
    H-6720 Szeged, Hungary
    Telephone: (+36) 62 545 119
    Fax number: (+36) 62 545 120
    E-mail: ist@puhe.szote.u-szeged.hu

CEJOEM 2000, Vol.6. No.2-3.:194-201

Key words:
Immunotoxicity, combined exposure, propoxur, cadmium, lead, rat

Abbreviations:
Cd = CdCl2
CdIT = Immunotoxic Dose of CdCl2
CdNOEL = Non-Observed Effect Level dose of CdCl2
DTH = delayed type hypersensitivity
IT = immunotoxic dose
MCV = mean cell volume of RBCs
NOEL = Non-Observed Effect Level 		Pb = lead acetate
PbIT = Immunotoxic Dose of lead acetate
PbNOEL = Non-Observed Effect Level of lead acetate
PFC = IgM-type haemolytic plaque forming cells
Px = propoxur
PxIT = Immunotoxic Dose of propoxur
PxNOEL = Non-Observed Effect Level of propoxur










Abstract:
The immunotoxic effects of 28-day combined oral exposure with the carbamate-type insecticide propoxur (Px) and two heavy metals, cadmium (Cd) and lead (Pb), were investigated in male outbred Wistar rats. In the present study, the immunotoxic dose (IT) of Px (8.51 mg/kg) was combined with non-observed effect level (NOEL) doses of CdCl2 (1.61 mg/kg) or lead acetate (20.0 mg/kg), and IT doses of CdCl2 (6.43 mg/kg) or lead acetate (80.0 mg/kg) were combined with the NOEL dose of Px (0.851 mg/kg). The IT and NOEL doses of the three substances were determined in preliminary experiments. To examine the interactions, general toxicological (body weight gain, organ weights of brain, thymus, lung, heart, spleen, liver, kidneys, adrenals, testicles, and popliteal lymph node), hematological (WBC and RBC count, Ht, MCV, cell content of femoral bone marrow), and immune function parameters (PFC assay, DTH reaction) were determined on the 29th day. Significant changes in any parameter of the groups treated with the combinations versus the internal control (treated with the high dose component of the combination alone) were considered as interactions.
    In the toxicological and hematological investigations interactions were observed in the relative weight of some organs in case of certain combinations. Body weight gain and the hematological parameters were, however, not affected. The humoral immune response (PFC assay) was suppressed by Px (IT) alone, and the immunosuppression became stronger when Px (IT) was combined with Pb (NOEL). In DTH reaction (one main route of cellular immune response) interactions were not found.
    The results suggest that the interactions between Px and the heavy metals examined can modify the toxicity and/or detection limits of the substances on their own, which can lead to false results in human epidemiological studies.

Received:  31 July 2000
Accepted:  01 December 2000
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