The Journal “Toksikologicheskiy vestnik” (Toxicological Review)
Critical parameters of the distributions rates of inhibition of tumor growth (ITG) indices and increasing median survival (IMS), which are adopted in pre-clinical practice for evaluation of the anticancer potential of original substances were accurately ascertained in experiments in vivo . Under the package Mathematica 9, software modules were created which allowed to assess the statistical reliability of the ITG indicator at the levels of 70% and 90 %, and the IMS rate at the levels of 50 % and 75 %, to calculate the mathematical expectation and confidence intervals for ITG and IMS indicators at any level of the effect, to compare the effectiveness of several drugs based on mathematical expectations and confidence intervals calculated for their ITG and IMS indicators in case of close location of the corresponding formal values, and carry out priori tests on the significance of ITG and IMS taking into account the main influencing factors: variation of parameters in experimental groups and size of experimental and control groups.
Keywords: rate of inhibition of tumor growth (ITG), rate of increase in lifespan (median survival), standard deviation (SD), expectation (ME), confidence intervals, t-student distribution, normal distribution, cumulative distribution function, probability density function
The effect of the Pelixim antidote on the possibility to detect markers of G type nerve agents sarin and soman was studies in bio probes obtained in an acute in vivo experiment after exposure of rats to organophosphorus nerve agents in doses of 0.5LD50. It was found out that the intake of equitoxic doses of soman and sarin leads to a decrease of acetylcholinesterase erythrocyte membrane (AChE) activity for up to 7 days after exposure. The effect of Pelixim on the recovery of erythrocyte AChE activity is mostly pronounced a day after sarin poisoning. The fluoride regeneration of nerve agents from blood plasma protein adducts was possible for up to 7 days after soman poisoning without antidotal therapy and for 3 days after with antidotal therapy; in case of sarin intoxication, fluoride regeneration was possible for 3 days regardless of the use of antidotal therapy . The antidote strongly affected the excretion of hydrolytic metabolite of sarin О-isopropyl methylphosphonic acid (IMPA) and had no effect on the excretion of hydrolytic metabolite of soman О-pinacolyl methylphosphonic acid (PMPA). A day after poisoning and Pelixim injection, IMPA was detected in urine at a level of 15.3 ng/ml, whereas its level in the urine samples of animals in the absence of antidotal therapy was 55.0 ng/ml; 3 days after poisoning, IMPA was detected at a level of 4.9 ng/ml exclusively in the urine of animals subjected to antidotal therapy. The urine levels of PMPA in animals subjected and not subjected to antidotal therapy were respectively 44 and 53 ng/ml a day after poisoning and 12 and 14 ng/ml respectively 3 days after poisoning. Thus, the antidote impact on the excretion profile of hydrolytic metabolites is more significant for sarin than that of soman.
Keywords: chemical toxicological analysis, organophosphorus nerve agents, sarin, soman, cholinesterases, markers, gas chromatography–mass spectrometry, antidotal therapy
Female white rats were exposed in a «nose only» inhalation device to an aerosol containing predominantly submicron (nanoscale included) particles of amorphous silica in a total concentration of 2.6±0.6 or 10.6±2.1 mg/m3, 4 h/day, 5 times a week, during up to 6 months. In an auxiliary experiment with a single-shot intratracheal instillation of these particles, it was shown that they induced a pulmonary cell response comparable with that when administrated a highly cytotoxic and fibrogenic standard quartz dust DQ12. However in a long-term inhalation test, the aerosol investigated proved to be of a very low systemic toxicity and fibrogenicity. This paradox may be explained by a low retention of SiO2 in lungs and other organs due to a relatively high in vivo solubility of those nanoparticles. Nevertheless their genotoxic action and transnasal penetration into the brain urge caution when assessing occupational or environmental hazard of that aerosol.
Keywords: nano-silica-containing industrial aerosol, long-term inhalation exposure, toxicity, fibrogenicity, toxicokinetics
In experiments on outbred albino rats, it was established that subacute intoxication with ethylene chlorohydrin (0.2 LD50 daily for 4 days) causes a decrease in Th1 and Th2 lymphocytes function to the same extent, diminishes parameters of humoral and cellular immune responses and the content of immunoregulatory cytokines IFN- , IL-2, IL-4 in blood, increases concentrations of pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10.
Keywords: ethylene chlorohydrin, Th1-, Th2-lymphocytes, immunotoxicity, cytokines
For the first time, the chronic inhalation effect of aliphatic hydrocarbons (HC) in low concentrations on metabolic profiles of low molecular weight organic compounds including free (FFA) and esterified (EFA) fatty acids in rats brain and liver was studied. Gas and liquid chromatography-mass spectrometry was used as analytical methods. The list of hydrocarbons includes hexane, heptane, octane, nonane and decane in various ratios. Changes in profiles of low-molecular compounds in the brain were detected under the action of a mixture of HCs in a concentration of 160 ± 20.5 mg/m3 for 90 days, while the action of the HCs mixture at lower concentrations of 31.4 ± 5.6 mg/m3 and 5.2 ± 1.08 mg/m3 only leads to minor changes in profiles. A significant increase in lysophospholipids concentrations, mainly of lysophosphatidylcholine, in the extract from the brain and blood plasma was revealed. The increase in the content of lysophospholipids in brain tissues can be considered as a consequence of the destruction of cell membranes, specific to neurodegenerative processes. At the same time, an increase in the lysophosphatidylcholine concentration in the brain is accompanied by a statistically significant decrease in the concentration of glycerol-3-phosphate and is not followed by changes in the concentrations of glycerophosphocholine, glycerophosphoethanolamine, choline, acetylcholine, FFA, or lysophosphatidic acid. It was shown that concentrations of lysophosphatidylcholine and lysophosphatidylethanamine, referred to the concentrations of glycerophosphocholine and glycerophosphoethanolamine in blood plasma, may serve as potential markers of the effect of HC on the brain.
Keywords: hydrocarbons, chronic effects, brain, liver, marker, lysophosphatidylcholines, chromatography-mass spectrometry
In experimental studies on rats (males, females) at their infantile stage starting from 10 days, a potential delayed toxic effect of the antiviral drug Kagocel on the reproductive system was studied. The drug was administered for 12 days in a therapeutic dose and at a dose 10-fold higher than the therapeutic one. Reproductive safety was estimated after animals reached the reproductive age (2.5 months). It was found out that the drug, when administered in both doses, does not decrease the fertility of animals, does not induce morphological and pathological changes in the sex glands, and does not have toxic effect on the offspring. Obtained data characterize Kagocel as a preparation with a wide reproductive safety profile and show that it can be used in pediatric practice for infants.
Keywords: Kagocel preparation, infantile age, (male, female rats, ) reproductive toxicity
Investigation results are reported on immunobiochemical indices in carassius carassius at a chronic exposure to sub-lethal Zink ions concentrations. In blood serum and liver, the following characteristics were investigated: antimicrobial properties, proportion of immune- deficient animals, content of non specific immune complexes, common lipids level, content of lipids peroxidation products and antioxidant activity. The relation between magnitudes of indices under investigation in fishes and the duration of their presence under experimental conditions is shown.
Keywords: carasius carassius, Zink ions, humoral immunity, lipids, pro-oxidant and antioxidant system
The article is devoted to the study of toxic effect of a new complex liquid mineral fertilizer «Agromineral» on the organism of laboratory animals. Results of sanitary and toxicological studies on assessment of toxicity and hazard of the agrochemical were analyzed ; based on investigation results, parameters of acute and subacute toxicity are established; irritating effects on skin and mucous membranes, cumulative effect, sensitizing effect were studied.
Keywords: agrochemical, toxicity, irritant effect, cumulative effect, sensitizing effect
Based on experimental results, toxicological assessment of the biological product oil-destructor «Lenoil»® – NORD, SHP is reported.. The biological product is intended for cleaning of oil-polluted soils and water objects at low positive temperatures. It was found out that the median lethal dose (LD50) at intragastric intake amounts to more than 5000 mg/kg, therefore the biological product refers to hazard class 4 (low hazardous substances). The biological product does not cause signs of irritation of respiratory tracts, but is able to induce slight irritation of eye mucous membranes and skin ( repeated applications).The biological product has no sensitizing action when reproducing a delayed-type hypersensitivity reaction. The biological product oil-destructor “Lenoil»® – NORD, SHP can be used for its intended purpose, i.e. to accelerate the destruction of oil and petroleum products during the remediation of oil-contaminated sites. At work the personnel must be provided with special clothing and personal protective equipment and observe hygiene and sanitary norms.
Keywords: biological product oil-destructor «Lenoil»® – the NORD, SHP, hazard class, inhalation toxicity, irritating and sensitizing action