The level and duration of protective immunity are often analyzed qualitatively or semi-quantitatively. The same strategy is applied to the analysis of antibody dynamics. At some point in time t after exposure or immunization, the presence of immunity against the infection is inferred from the level of specific antibodies by comparing it to a reference value. This approach does not account for the stochastic nature of human disease after exposure to a pathogen. At the same time, it is not fully clear what antibody level should be considered protective. The aim of this study was to develop a mathematical model for quantitative determination of protective immunity against SARS-CoV-2 and its duration. We demonstrate that the problem of describing protective immunity in quantitative terms can be broken down into 2 interrelated problems: describing the quantitative characteristics of a pathogen’s virulence (in our case, the pathogen is SARS-CoV-2) and describing the dynamics of antibody titers in a biological organism. Below, we provide solutions for these problems and identify parameters of the model which describes such dynamics. Using the proposed model, we offer a theoretical solution to the problem of protective immunity and its duration. We also note that in order to quantitatively determine the studied parameters in a homogenous population group, it is necessary to know 5 parameters of the bivariate probability density function for correlated continuous random variables: the infective dose of the pathogen and the antibody titer at which the disease develops and which are still unknown.
Wipe sampling is widely used for microbiological control purposes. Sanitary and chemical studies also include analysis of samples wiped from the work surfaces during routine and periodic working conditions safety inspections at chemical facilities. The analysis also allows assessing the toxicity and hazard of items/structures that could be in contact with highly toxic substances. This study aimed to investigate the capabilities and limitations of the surface wipe sample analysis method in control of residual contamination of equipment and building structures of a former chemical weapons destruction facilities (CWDF) with sulfur mustard and O-isobutyl-S(2-diethylaminoethyl) methylphosphonothioate (VR), as well as their degradation products. Gas chromatography with tandem mass spectrometry (GC-MS/MS) enabled identification of the sulfur mustard markers, high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) allowed identifying VR markers. An assessment of the matrix influence on the results of GC-MS/MS and HPLC-MS/MS analysis was carried out. The matrix effect was established to affect the results the most in case of HPLC-MS/MS analysis: for GC-MS/MS analysis of target substances, the matrix factor averaged at 60–80%, for HPLC-MS/ MS it was less than 40%. The average percent sulfur mustard recoveries from three types of surfaces (PVC tiles, laminate and metal plates) was 9 ± 2%, 0.13 ± 0.02% and 0.10 ± 0.03%; in case of VR, the recoveries was 2.7 ± 0.5%, 11.8 ± 0.3% and 0.8 ± 0.1%, respectively. The limits of detection for sulfur mustard by GC-MS/MS and VR by HPLC-MS/MS were established at 0.001 MPL and 0.02 MPL, respectively. The developed approaches were applied to the analysis of wipe samples from the surfaces of the equipment and engineering structures of the former CWDF.
After elimination of the chemical weapons, it is necessary to relieve the consequences of operation of the chemical weapons destruction facilities (CWDF). This study aimed to assess the results of such relieve activities from the hygienic point of view. The assessment allows considering partial conversion of the CWDFs' infrastructure for civil purposes. At four CWDFs, the sites of contamination of equipment and infrastructural components with degradition products of organophosphorous agents (OPA) and blister agents (BA) were identified. The technologies that enabled analysis of the samples taken were high performance liquid chromatography with tandem mass spectrometry, gas chromatography–mass spectrometry, gas chromatography–tandem mass spectrometry, and atomic absorption spectroscopy with electrothermal atomization. The analysis revealed contamination of building structures, equipment, utility lines, waterproofing, heatinsulating, and other materials inside the CWDF process buildings, regardless of their purpose, with OPA and BA degradation products. In the absence of hygienic standards and information on their toxicity, it was impossible to assess the hazard thereof. In all the samples taken, the residual content of toxic substances was below the limit of detection of the measurement methods applied, i.e., none was found. The article presents a methodology for a stepwise hygienic assessment of the CWDF infrastructure to be converted and develops recommendations for its subsequent safe use. The conclusions state expediency of development of hygienic standards for the OPA and BA degradation products and development and certification of the relevant measurement procedures.
As a result of the industrial purification of hydrocarbons from mercaptans, tens of thousands of tons of dialkyl disulphides and their mixtures, the toxicity and hazard of which has not been fully understood, are accumulated annually. The exposure standards have been developed only for dimethyl disulphide. The study was aimed to define toxicometry parameters for diethyl disulphide, disulphide oil, and the mixture of dialkyl disulphides. Toxicology studies involving male outbred rats made it possible to define the median lethal doses and concentrations: diethyl disulphide — after intragastric injection DL50 = 1575 mg/kg, after the 4-hour inhalation exposure CL50 = 18,700 mg/m3, after intraperitoneal injection DL50 = 1134 mg/kg, and after skin application DL50 ˃ 2500 mg/kg; mixture of dialkyl disulphides — after intragastric injection DL50 = 428 mg/kg, after the 4-hour inhalation exposure CL50 = 4510 mg/m3, after intraperitoneal injection DL50 = 212 mg/kg, and after skin application DL50 ˃ 2500 mg/kg; disulphide oil — after intragastric injection DL50 = 448 mg/kg, after the 4-hour inhalation exposure CL50 = 4534 mg/m3, after intraperitoneal injection DL50 = 156 mg/kg, and after skin application DL50 ˃ 2500 mg/kg. The hazard assessment for dialkyl disulphides and their mixtures was performed.
To date, there have been no exposure standards for air concentrations of 1,4-dichlorohexafluorobutene (DCHF) in the work areas. The study was aimed to assess the toxicity of DCHF and to evaluate health hazard in acute, subacute, and chronic experiments. It was found that the substance was highly hazardous, DL50 in mice after intragastric injection was 79.0 mg/kg, СL50 was 229.0 mg/m3, and in rats these values were 86,0 mg/kg and 670,0 mg/m3. In animals, DCHF had a moderate local irritative effect on animal skin and ocular mucous membranes, as well as the skin resorptive effect. The 18.2 mg/m3 threshold limit concentration for a single inhalation exposure to DCHF was defined based on the changes in behavior responses and blood parameters. The 30-day subacute inhalation experiment revealed the pronounced cumulative effect of the substance. The 4-months chronic inhalation study showed that the exposure of experimental rats to 16.8 mg/m3 concentration of DCHF resulted in impaired function of central nervous system and cardiac activity, altered hematologic, biochemical, acid-base, and blood gas values, as well as in morphological alterations in lungs, which persisted after the 30-day recovery period. The chronic exposure threshold defined for DCHF was 2.2 mg/m3, and the defined no observable effect level was 0.24 mg/m3. Based on the study results, the maximum permissible concentration of DCHF in the air of the working area of 0.2 mg/m3 was confirmed and approved, the substance was assigned hazard class 2, vapor + aerosol + (specific protection of skin and eyes required). Gas chromatographic method using electron-capture detection for determination of DCHF mass air concentration in the work areas has been developed and approved.
External quality control in the form of interlaboratory comparisons (ILCs) is an important criterion of the testing laboratory competence. The study was aimed to summarize the approaches to developing objects for proficiency testing (OPT) based on physical simulation of acoustic noise sources, airborne ultrasound, vibration, and the practice of their use for ILC. Analysis of the OPT effectiveness based on physical simulation of factors, the test benches (TBs), was performed based on their testing and certification results, as well as on the results of appropriate ILCs. The results of using TB as OPT are considered for the following factors: acoustic noise, airborne ultrasound, and vibration. When measuring acoustic noise, TB played back the acoustic noise record with high stability. ILC involving measurement of airborne ultrasound was performed the same way, however, the frequency of the acoustic signal being reproduced was in the range of 11–22 kHz. TBs, based on a manual mechanized tool and a platform equipped with electromechanical agitator, were developed for ILC involving the measurement of local and general vibration. Stability of vibration generated was provided by means of the automated system for maintaining the set level with feedback and proportional integral derivative (PID) controller. When arranging and performing ILCs involving measurement of noise and vibration, a crucial role is played by the methods developed specifically for ILCs, allowing one to take into account all the conditions that affect the measurement results.