The present study was performed to assess the effect of the petrochemical sludge application rate on the mutagenic activity (Ames test) of soil and the persistence of mutagenic activity during laboratory soil bioremediation process. Sludge-soil systems were prepared at four different sludge application rates (1.25, 2.5, 5, and 10% w/w). Unamended soil was used as a control. Immediately following sludge application, in the absence or presence of S9, a linear correlation between sludge application rates and mutagenicity was found but differed significantly (p < 0.05) from the control system only at higher application rates (5 and 10% w/w). The direct mutagenicity of all systems decreases during the bioremediation process, and after a year of treatment only the 10% system induced a mutagenic response that was significantly different from the control system. On the other hand, an initial increase of the indirect mutagenicity was observed at all application rates. The time required for observing this increase was inversely proportional to the initial sludge concentration. After a year of treatment, the indirect mutagenicity of all sludge-amended soils was not significantly different but was significantly different from the unamended soils. The persistence of the direct mutagenic activity of the sludge-amended soils was related to the sludge concentration, whereas the indirect mutagenic persistence was related to the relationship between easily degradable hydrocarbons and polynuclear aromatic hydrocarbons concentration and independent from the initial application rate.
Recently published data indicates that high ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM either orally (0.2 mg/kg) or by one or two nasal spray doses. The overall safety, and histopathology of the IVM-spray application site tissues, were assessed. The IVM concentration profiles measured in plasma and respiratory tract tissues after the nasal spray were compared with those achieved after the oral administration. Animals tolerated well the nasal spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in nasopharyngeal and lung tissues. The nasal/oral IVM concentration ratios in nasopharyngeal and lung tissues markedly increased by repeating (12 h apart) the spray application. The fast attainment of high and persistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oral route. These original results support the undertaking of future clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the prevention and/or treatment of COVID-19.
: Bioremediation is capable of reducing the hydrocarbon concentration of contaminated soil by 75È95% depending on the soil type, the kind of hydrocarbons and the history of the contamination. The impact of di †erent number of petrochemical sludge applications to soil on the degree of PAH elimination was assessed. A simple and reliable extraction and gas chromatographic method was used to facilitate more rapid determination of hydrocarbon contamination in soils and sludge wastes. Its application in a model laboratory bioremediation experiment and a pilot Ðeld study were used to illustrate its practical beneÐts. Post-remediation persistence of sludge constituents was evaluated after a single dose sludge application in the laboratory and after seven sludge applications in the Ðeld. A relative increase in the concentration of some PAHs was detected at the end of the experiments, but their individual concentrations were reduced to suggested values for industrial soils. The remaining concentration of total hydrocarbons in soil was found to be similar in both experiments, pointing to soil organic matter adsorption capacity as the factor determining hydrocarbon elimination limits in soil bioremediation.
In many cases, petroleum‐derived sludges are stored in open air ponds. In this condition, weathering may produce changes that can be important when choosing a treatment and/or disposal method. The effect of weathering on chemical and toxicological characteristics of sludges were studied in two different sludges, one from a petrochemical API‐separator (API2N) and the other from a refinery biological treatment unit. Starting determinations were performed with end‐of‐the‐pipe composite samples. Determinations were repeated after a 6‐month weathering period. Physico‐chemical characterization included pH, water content, extractable organics, and class fractionation into aliphatics, aromatics, and asphaltics. Microbiological concentration was done by enumeration of viable bacteria in plate count agar and solid mineral medium with the sludge as the only source of carbon and energy, and fungi in Cooke rose bengal agar. For toxicological assessment a battery of bioassays was performed that included: Bacillus cereus spot test, Resazurine reduction test, Bioluminiscence test with Photobacterium, effects on viable soil bacteria counts, Latuca sativa seed germination and root elongation test. The Ames test (TA‐98 with S9 microsomal activation) was used to assess genotoxicity changes. Comparison of starting results of both sludges with those obtained after 6 months showed a minimal change in the chemical characteristics, a significant increase in the starting low level of bacteria in API2N, reduction in acute toxicity and increase in the mutagenic effect in the dimethyl sulfoxide (DMSO)‐sludges fraction, but not in the DMSO‐ethylether organic fraction in both sludges. ©1999 John Wiley & Sons, Inc. Environ Toxicol 14: 227–233, 1999
High ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray (NIVM spray) administration may contribute to attaining high drug concentrations in nasopharyngeal (NP) tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performance of a new NIVM spray formulation in a piglet model were assessed. Crossbred piglets (10/12 kg) were treated with either one or two (12 h apart) doses of N IVM spray (2 mg, 1 puff/nostril) or orally (0.2 mg/kg). The overall safety of NIVM-spray was assessed (clinical, haematological, serum biochemical determinations), and histopathology evaluation of the application site tissues performed. The IVM concentration profiles measured in plasma and respiratory tract tissues (nasopharynx and lungs) after the nasal spray treatment (one and two applications) were compared with those achieved after the oral administration. Animals tolerated well the novel NIVM spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in NP and lung tissues. Significant increases in IVM concentration profiles in both NPtissue and lungs were observed after the 2 dose nasal administrations. The nasal/oral IVM concentration ratios in NP and lung tissues (at 6 h postdose) markedely increased by repeating the spray application. The fast attainment of high and persistent IVM concentrations in NP tissue is the main advantage of the nasal over the oral route. These original results are encouraging to support the undertaking of further clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the treatment and/or prevention of COVID-19.
The present study was performed to assess the effect of the petrochemical sludge application rate on the mutagenic activity (Ames test) of soil and the persistence of mutagenic activity during laboratory soil bioremediation process. Sludge-soil systems were prepared at four different sludge application rates (1.25, 2.5, 5, and 10% w/w). Unamended soil was used as a control. Immediately following sludge application, in the absence or presence of S9, a linear correlation between sludge application rates and mutagenicity was found but differed significantly (p < 0.05) from the control system only at higher application rates (5 and 10% w/w). The direct mutagenicity of all systems decreases during the bioremediation process, and after a year of treatment only the 10% system induced a mutagenic response that was significantly different from the control system. On the other hand, an initial increase of the indirect mutagenicity was observed at all application rates. The time required for observing this increase was inversely proportional to the initial sludge concentration. After a year of treatment, the indirect mutagenicity of all sludge-amended soils was not significantly different but was significantly different from the unamended soils. The persistence of the direct mutagenic activity of the sludge-amended soils was related to the sludge concentration, whereas the indirect mutagenic persistence was related to the relationship between easily degradable hydrocarbons and polynuclear aromatic hydrocarbons concentration and independent from the initial application rate.
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