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.
VIEWS 2114
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.
VIEWS 2225
The development of coronavirus infection outbreak into a pandemic, coupled with the lack of effective COVID-19 therapies, is a challenge for the entire pharmaceutical industry. This study aimed to assess the treatment and preventive efficacy of the amino acid-peptide complex (APC) in male Syrian hamsters infected with SARSCoV-2 (intranasal administration of 26 μl of the virus culture, titer of 4 × 104 TCD50/ml). In a modeled COVID-19 case, APC administered for treatment and preventive purposes reduced lung damage. Compared to the positive control group, test group had the lung weight factor 15.2% smaller (trend), which indicates a less pronounced edema. Microscopic examination revealed no alveolar edema, atypical hypertrophied forms of type II alveolocytes, pulmonary parenchyma fibrinization. The macrophage reaction intensified, which is probably a result of the APC-induced activation of regenerative processes in the lung tissues. Spleens of the animals that received APC for therapeutic and preventive purposes were less engorged and had fewer hemorrhages. The decrease of body weight of the test animals that received APC for treatment and prevention was insignificant (p < 0.05), which indicates a less severe course of COVID-19. Administered following a purely therapeutic protocol, APC proved ineffective against SARS-CoV-2 post-infection. Thus, APC-based drug used as a therapeutic and preventive agent reduces pulmonary edema and makes morphological signs of lung tissue damage less pronounced in male Syrian hamsters infected with SARS-CoV-2.
VIEWS 2415
Low molecular weight compounds targeting chaperone proteins Hsp90 and Hsp70 have opened up a new avenue in the therapy of neoplasms. In 2020, we tested 3 Hsp70 inhibitors from the class of 4-aminopiperidine derivatives for their antitumor activity on in vivo models. The list of the tested compounds included N-(2-chlorobenzyl)-N-ethyl-1-(2-(methylthio)pyrimidin-4-yl)piperidin-4-amine (compound 1), 4-((methyl(1-(2-(methylthio)pyrimidin-4-yl) piperidin-4-yl)amino)methyl) benzonitrile (compound 2) and N-(2,6- dichlorobenzyl)-1-(1-(2-(ethylthio)pyrimidin-4-yl)piperidin-4-yl)-N-methylmethaneamine (compound 3). The aim of this study was to compare the efficacy of 4-aminopiperidine derivatives in vivo using the models of transplantable murine L1210 lymphocytic leukemia and B16 melanoma. Compounds 2 and 3 used in combination with cyclophosphamide exhibited high cytotoxic activity (р = 0.05) against L1210 leukemia (an 80-82% increase in survival time) and B16 melanoma (98-99.7% tumor growth delay). For L1210 lymphocytic leukemia, compounds 2 and 3 used in combination with cyclophosphamide fell into the low (+) therapeutic potential category. For B16 melanoma, compounds 1, 2 and 3 used in combination with cyclophosphamide fell into either low (+) or moderate (++) therapeutic potential categories. On the whole, the tested doses of the compounds used in combination with cyclophosphamide hold promise for the therapy of L1210 leukemia and B16 melanoma in mouse models. Our findings confirm the potential of low molecular weight Hsp70 inhibitors for combination chemotherapy against cancer.
VIEWS 2315