Three different insecticides: dimethoate, cypermethrin and amitraz were given, alone or combined with the heavy metals Pb, Hg and Cd, to male Wistar rats per os for 12 weeks from their 4th week of life. After the treatment period, the left hemisphere of the rats was exposed in urethane anaesthesia, and spontaneous and evoked cortical activity was recorded from the primary sensory areas. The effects of dimethoate on the spontaneous activity, and of dimethoate and amitraz on the evoked responses, were increased by the metal combination treatment, whereby the metals alone had no effect on the spontaneous and mild effect on the evoked activity. Finally, the animals were dissected, organ weights measured, and relative organ weights calculated. The weight gain of all treated groups was significantly retarded compared to the control. Several organ weights were also significantly reduced, mainly in groups receiving insecticide plus metal treatment. The toxic interactions observed in this work indicate that combined human exposure to environmental pesticide residues and heavy metals may have unexpectedly severe effects.
Atabek, M. E., Aydin, K., Erkul, I. (2002) Different clinical features of amitraz poisoning in children. Hum. Exp. Tox. 21, 13–16.
Boyes, W. K., Moser, V. C. (1987) Investigations of amitraz neurotoxicity in rats, II. Effects on visual evoked potentials. Fundam. Appl. Toxicol. 9, 140–153.
Braga, M. F. M., Pereira, E. F. R., Albuquerque, E. X. (1999) Nanomolar concentrations of lead inhibit glutamatergic and GABAergic transmission in hippocampal neurons. Brain Res. 826, 22–34.
Brookes, N. (1992) In vivo evidence for the role of glutamate in the CNS toxicity of mercury. Toxicolog. 76, 245–256.
Büsselberg, D. (1995) Calcium channels as target sites of heavy metals. Toxicol. Lett. 82, 255–261.
Costa, L., Olibet, G., Wu, D. S., Murphy, S. D. (1989) Acute and chronic effects of the pesticide ami-traz on alpha 2-adrenoceptors in mouse brain. Toxicol. Lett. 47, 135–143.
Dési, I., Dobronyi, I., Varga, L. (1986) Immuno-, neuro- and general toxicologic animal studies on a synthetic pyrethroid, cypermethrin. Ecotoxicol. Environ. Saf. 12, 220–232.
Dési, I., Nagymajtényi, L., Schulz, H., Papp, A. (1998) Experimental model studies of pesticide exposure. NeuroToxicol. 19, 611–616.
Dwivedi, C., Raghunathan, R., Joshi, B. C., Foster, H. W. (1980) Effect of mercury compounds on acetylcholin transferase. Res. Commun. Chem. Pathol. Pharmacol. 30, 381–384.
Elinder, C. G. (1985) Cadmium: Uses, occurrence and intake. In: Friberg, L., Elinder, C. G., Kjellström, T. (eds) Cadmium: Uses, Occurrence and Uptake, vol. 1. CRC Press, Boca Raton, Florida, pp. 23–64.
Florio, J. C., Sakate, M., Palermo-Neto, J. (1993) Effects of amitraz on motor function. Pharmacol. Toxicol. 73, 109–114.
Gilbert, M. E., Dyer, R. S. (1988) Increased hippocampal excitability produced by amitraz. Neuro-toxicol. Teratol. 10, 229–235.
Gralewicz, S., Tomas, T., Górny, R., Kowalczyk, W., Socko, R. (1991) Changes in brain bioelectri-cal activity (EEG) after repetitive exposure to an organophosphate anticholinesterase. II. Rat. Polish J. Occup. Med. Environ. Healt. 4, 183–196.
Grandjean, P. (1978) Regional distribution of lead in human brains. Toxicolog. 2, 65–69.
Institóris, L., Papp, A., Siroki, O., Banerjee, B. D., Dési, I. (2002) Immuno- and neurotoxicological investigation of combined subacute exposure with the carbamate pesticide propoxur and cadmium in rats. Toxicolog. 178, 161–173.
Institóris, L., Siroki, O., Dési, I. (2001) Immunotoxicological investigation of subacute combined exposure by permethrin and the heavy metals arsenic(III) and mercury(II) in rats. Int. Immuno-pharmacol. 1, 925–933.
Institóris, L., Siroki, O., Űndeger, Ű., Basaran, N., Dési, I. (2001) Immunotoxicological investigation on rats treated subacutely with dimethoate, As3+ and Hg2+ in combination. Hum. Exp. Toxicol. 20, 329–336.
Institóris, L., Siroki, O., Űndeger, Ű., Dési, I., Nagymajtényi, L. (1999) Immunotoxicological effects of repeated combined exposure by cypermethrin and the heavy metals lead and cadmium in rats. Int. J. Immunopharmacol. 21, 735–743.
Jiang, H. M., Han, G. A., He, Z. L. (1990) Clinical significance of hair cadmium content in the diagnosis of mental retardation of children. Chin. Med, J. (Engl., 103, 331–334.
Lille, F., Hazemann, P., Garnier, R., Dally, S. (1988) Effects of lead and mercury intoxications on evoked potentials. J. Toxicol. Clin. Toxicol. 26, 103–116.
Metherate, R., Cox, C. L., Ashe, J. H. (1992) Cellular bases of neocortical activation: modulation of neural oscillations by the nucleus basalis and endogenous acetylcholine. J. Neurosc. 12, 4701–4711.
Moser, V. C., McPhail, R. C. (1989) Investigations of amitraz neurotoxicity in rats, III. Effects on motor activity and inhibition of monoamine oxidase. Fundam. Appl. Toxicol. 12, 12–22.
Müller, M., Anke, M. (1994) Distribution of cadmium in the food chain (soil-plant-human) of a cadmium exposed area and the health risks of the general population. Sci. Total Environ. 156, 151–158.
Muttray, A., Padberg, F., Jung, D., Rohlfing, H. R., Schulz, M., Konietzko, J. (1996) Acute changes in human EEG after exposure to low doses of oxydemeton methyl. Centr. Eur. J. Occup. Environ. Med. 2, 367–378.
Nagymajtényi, L., Schulz, H., Papp, A., Dési, I. (1997) Behavioural and electrophysiological changes caused by subchronic lead exposure in rats. Centr. Eur. J. Occup. Environ. Med. 3, 195–209.
Papp, A., Pecze, L., Vezér, T. (2004) Comparison of the effect of subacute organophosphate exposure on the cortical and peripheral evoked activity in rats. Pest. Biochem. Physiol. 79, 94–100.
Papp, A., Pecze, L., Vezér, T. (2002) Central neurotoxic effects elicited with three organophosphorus compounds: comparison of acute and subchronic administration. Fiziologia (Timisoara. 12, 19–24.
Papp, A., Pecze, L., Vezér, T. (2005) Acute effects of lead, mercury and manganese on the central and peripheral nervous system in rats in combination with alcohol exposure. Arh. Hig. Rada Toksikol. (Zagreb. 56, 241–248.
Papp, A., Vezér, T., Pecze, L. (2002) Effects of inorganic and organic mercury on cortical and hip-pocampal activity in rats. Centr. Eur. J. Occup. Environ. Med. 8, 118–125.
Piikivi, L., Tolonen, U. (1989) EEG findings in chloralkali workers subjected to low long term exposure to mercury vapour. Br. J. Ind. Med. 46, 370–375.
Schulz, H., Nagymajtényi, L., Papp, A., Dési, I. (1997) Behavioural and neurophysiological consequences of subchronic mercury exposure in rats. Centr. Eur. J. Occup. Environ. Med. 3, 210–223.
Soderlund, D. M., Bloomquist, J. R. (1989) Neurotoxic actions of the pyrethroid insecticides. Ann. Rev. Entomol. 34, 77–96.
Suszkiw, J., Toth, G., Murawsky, M., Cooper, G. P. (1984) Effects of Pb2+ and Cd2+ on acetylcholine release and Ca2+ movements in synaptosomes and subcellular fractions from rat brain and torpedo electric organ. Brain Res. 323, 31–46.
Vataev, S. I., Malgina, N. A., Oganesian, G. A. (1994) The effect of cadmium on the structure of the circadian cycle of waking-sleep and on the EEG in Wistar rats. Zh. Evol. Biokhim. Fiziol. 30, 408–419. (In Russian)
Viaene, M. K., Masschelein, R., Leenders, J., De Groof, M., Swerts, L. J., Roels, H. A. (2000) Neurobehavioural effects of occupational exposure to cadmium: a cross sectional epidemiological study. Occup. Environ. Med. 57, 19–27.
Vijverberg, H. P. M., van den Bercken, J. (1990) Neurotoxical effects and the modes of action of pyrethroid insecticides. Crit. Rev. Toxicol. 21, 105–126.
Winneke, G., Altmann, L., Kramer, U., Turfeld, M., Behler, R., Gutsmuths, F. J., Mangold, M. (1994) Neurobehavioral and neurophysiological observations in six year old children with low lead levels in East and West Germany. NeuroToxicol. 15, 705–713.
Supported by an OTKA grant, No. T042955.
About this article
Cite this article
Lengyel, Z., Lukács, A., Szabó, A. et al. Neurotoxic and General Effects of Combined Subchronic Exposure of Rats to Insecticides and Heavy Metals. BIOLOGIA FUTURA 57, 423–432 (2006). https://doi.org/10.1556/ABiol.57.2006.4.4
- heavy metal