Background. The study of the biological mechanisms of action and safety of polymers is an actual multidisciplinary problem. The growth of volume and expansion of the scope of new compositions application increases chemical hazards and negative consequences to public health, despite their attributing to the factors of low intensity.
The purpose of the study was to conduct comparative evaluation of isolated and combined action of polymer components on sympathoadrenal system, the allocation of informative biomarkers and use them for hygienic standardization of new materials. Materials and methods. In chronic experiments on 32 white female rats the effect of the plasticizer dibutyl phthalate (DBP) and the flame retardant hexabromocyclododecane (HBCD) have been studied. The animals were injected intraperitoneally at a dose of DBP 1/10 DL50 (50,0 mg / kg) one time per week for 12 weeks plus 4 week recovery period (RP); HBCD – 500.0 mg / kg; DBP and HBCD mixture in similar doses; and group 4 – control. The content of catecholamine (CA) – epinephrine (E), norepinephrine (NE), dopamine (DA) and their precursor dihydroxyphenylalanine (DOPA) at the beginning of the experiment, after 4, 8, 12 weeks of exposure, and after 4 weeks of RP, in the urine and in adrenals (12 weeks) conducted at the spectrofluorimeter «Solar» CM 2203, Belarus. At 12 weeks the activity of monoamine oxidase (MAO – K.F.1.4.3.4) was also determined spectrophotometrically in the liver and brain using a photometer PD303UV, Japan.
Results and discussion. In the dynamics of the experiment the phase change of CA urinary excretion levels were revealed. During the 4th week of the exposition the marked increase in E in the urine of animals of all experimental groups, the most pronounced when the DBP + HBCD exposure (35.2 %). During the 8th week it stabilization of all indices was found, which are the signs of the primary adaptation. At the same time, the tendency to general activation of sympathoadrenal system (SAS): all examined CA levels growth in the urine and the reduction ratio of EN / E to 20,0 % (sign of hormonemediator dissociation). Most clearly this can be seen in the group of animals, exposed by DBP (p < 0.05), in which the opposite changes of NE and DA in the urine were found. During the 12th week of the experiment there was transition to a phase of exhaustion, which is characterized by the decrease of the EN and DA excretion and the (SAS) reserve reduction, in particular the synthesis and the urine level the predecessor CA – DOPA.
Under the combined action of DBP + HBCD these changes reached the maximum values. After 4 weeks of RP it was indicated partly recovery of studied indicators, for some of them – just as a trend. Content of neurotransmitters in adrenals was significantly different from the control and baseline values (p < 0,05), especially, when combined action DBP + HBCD. The obtained results correspond to the changes of MAO activity in tissues. When exposured to DBP it was most pronounced in the liver (general toxic effect), while the endocrine disruptor HBCD showed predominantly neurotoxic effects.
Chronic exposure to components of the polymeric materials causes a phase change in the content and the ratio of the CA and DOPA (as a sign of hormonal and mediator dissociation) with the depletion of functional reserves, particularly when combined action that may underlie the development of the pathology of chemical etiology. The components of sympathoadrenal system activity are the informative biomarkers of the toxicogenesis during the polymeric materials exposure.
Keywords: disregulation, sympathoadrenal system, polymeric materials, combined action
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