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The relevance of considering the problems and prospects of biological control is associated with the need to form scientific, methodological and organizational foundations for the inclusion of biological control of industrial exposure to harmful chemicals in the system of social and hygienic monitoring to ensure the chemical safety of the Russian Federation. The purpose of the work is to substantiate the need to develop and implement methodological recommendations for the development and validation of chromatographic methods for biological control of industrial exposure to harmful substances with the system of sanitary and epidemiological regulation of the Russian Federation. The published results of works in the department of toxicology of the "Research Institute of Hygiene, Occupational Pathology and Human Ecology", carried out under the guidance of the authors, were used, and a number of new additions to the toxicokinetic equations were made, in particular, a method for calculating the material cumulation coefficient (Km.cum) was proposed for the first time.
The relevance of considering the problems and prospects of biological control is associated with the need to form scientific, methodological and organizational foundations for the inclusion of biological control of industrial exposure to harmful chemicals in the system of social and hygienic monitoring to ensure the chemical safety of the Russian Federation. The purpose of the work is to substantiate the need to develop and implement methodological recommendations for the development and validation of chromatographic methods for biological control of industrial exposure to harmful substances with the system of sanitary and epidemiological regulation of the Russian Federation. The published results of works in the department of toxicology of the "Research Institute of Hygiene, Occupational Pathology and Human Ecology", carried out under the guidance of the authors, were used, and a number of new additions to the toxicokinetic equations were made, in particular, a method for calculating the material cumulation coefficient (Km.cum) was proposed for the first time.
Introduction. The introduction of metabolomic approaches into the practice of toxicological studies, as well as the expansion of the methodological capabilities of the laboratory for the determination of low-molecular, metabolic biomarkers of the effect, makes it possible to more effectively detect and identify new biomarkers. Material and methods. For metabolic profiling of blood plasma and urine samples, Shimadzu QP2010plus or Agilent 5975C gas chromatomass spectrometers were used. The results were processed using optimized databases of analytical characteristics of endogenous compounds and the AMDIS system; NIST/EPA/NIH 2017 was used to identify the detected compounds. Statistical processing was performed using Statistica. Results. A two-stage procedure for preparing blood plasma and urine samples for analysis by GC-MS was developed, a mixture of internal standards was selected, a list of compounds - endogenous metabolites was determined, and the metrological characteristics of their determination were evaluated. Limitations. The list of analytes suitable for determination by GC-MS is limited to volatile and conditionally volatile compounds. Conclusion. Using an optimized database of sample metabolites prepared for analysis according to a standardized procedure allows filtering out analytes with low reproducibility. Small (up to 100) chromatospectral databases make it possible to increase the reliability of identification, eliminate the effect of retention time drift, and, as a result, increase the statistical power of the entire experiment without increasing the number of laboratory animals.
Introduction. This paper considers aspects of the development of a toxicokinetically based model for scaling the limit concentrations of toxic compounds in the air, estimating the coefficients of their material cumulation, as well as estimating the concentrations of toxicants in biological media expected in the course of biological control. The results of testing the model on the example of organophosphorus pesticides (OP) and volatile industrial pollutants (VIP) are presented. Material and methods. For experimental modeling of intoxication, male chinchilla rabbits obtained from the Rappolovo nursery were used. Blood sampling was carried out from the marginal vein of the ear. For the highly sensitive determination of OP and VIP in biological samples, previously developed highly sensitive gas chromatographic techniques were used. Calculation of toxicokinetic parameters was made using a two-compartment model. Results. A toxicokinetically based model for scaling the limit concentrations of toxic compounds in the air, estimating the coefficients of their material cumulation, and estimating the concentrations of toxicants in biological media expected in the course of biological control is proposed. Research limitations. The proposed algorithm for scaling toxicokinetic parameters can be applied under the condition that the bioavailability of chemical compounds for the animal and human body is close, as well as the area under the toxicokinetic curve that is close to a linear dependence on the dose. Conclusion. Using the proposed toxicokinetically substantiated model for scaling the threshold concentrations, recommendations were made on chemical-analytical methods of biological control in the working area and atmospheric air for OP and VIP.
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