|
|
QSAR Analysis of the Acute Toxicity Indices Determined by Alternative Methods
Kanásová, Mária ; Rucki, Marian (advisor) ; Dvořáková, Markéta (referee)
1 Abstract The goal of the thesis is to determine acute toxicity indices of seven alcohols (2-ethoxyethanol, 1-propanol, 3-methyl-1-butanol, 3-methyl-2-butanol, 3-hexanol, 2-methyl-3-hexanol, 1-nonanol) by two different alternative methods. Another goal is to create QSAR models to predict the acute toxicities of alcohols which belong into model limits. First of the methods used is based on the movement inhibition of lower animals Tubifex tubifex. The method provides the acute toxicity indices EC50. The second method uses the cell line of mouse fibroblasts called Balb/c 3T3 and it provides the acute toxicity indices IC50. The IC50 were recalculated to the LD50 values that correspond to the oral administration of alcohols to a rat. It has been found that 1-nonanol is included into the category of alcohols classified as acute oral toxic according to the EU CLP system. Other six alcohols are non-classified as acute oral toxic. Subsequently, accurate QSAR models has been created in order to predict the acute toxicity of other alcohols using Tubifex tubifex specie or Balb/c 3T3 cell line. The models are suitable for saturated, branched, ethoxy- and cyclic alcohols with the log POW value from −0.74 to 3.07. It was necessary to exclude the acute toxicity indices of 1-nonanol from these models as some solubility...
|
|
|
QSAR Analysis of the Acute Toxicity Indices Determined by Alternative Methods
Kanásová, Mária ; Rucki, Marian (advisor) ; Dvořáková, Markéta (referee)
1 Abstract The goal of the thesis is to determine acute toxicity indices of seven alcohols (2-ethoxyethanol, 1-propanol, 3-methyl-1-butanol, 3-methyl-2-butanol, 3-hexanol, 2-methyl-3-hexanol, 1-nonanol) by two different alternative methods. Another goal is to create QSAR models to predict the acute toxicities of alcohols which belong into model limits. First of the methods used is based on the movement inhibition of lower animals Tubifex tubifex. The method provides the acute toxicity indices EC50. The second method uses the cell line of mouse fibroblasts called Balb/c 3T3 and it provides the acute toxicity indices IC50. The IC50 were recalculated to the LD50 values that correspond to the oral administration of alcohols to a rat. It has been found that 1-nonanol is included into the category of alcohols classified as acute oral toxic according to the EU CLP system. Other six alcohols are non-classified as acute oral toxic. Subsequently, accurate QSAR models has been created in order to predict the acute toxicity of other alcohols using Tubifex tubifex specie or Balb/c 3T3 cell line. The models are suitable for saturated, branched, ethoxy- and cyclic alcohols with the log POW value from −0.74 to 3.07. It was necessary to exclude the acute toxicity indices of 1-nonanol from these models as some solubility...
|
|
|
Separation of toxicologically relevant arsenic species for speciation analysis by RP-HPLC-ICP-MS
Kanásová, Mária ; Matoušek, Tomáš (advisor) ; Červený, Václav (referee)
The thesis is mapping possibilities of separation of toxicologically relevant arsenic species complexed with peptides by reversed-phase high-performance liquid chromatography-inductively coupled plasma mass spectrometry (RP-HPLC-ICP-MS). The C18 chromatography column and gradient elution of the mobile phase (0,1% formic acid with gradient of acetonitrile) was used. At these conditions the separation of simple arsenic species - arsenite (As(III)), arsenate (As(V)), monomethylarsenic acid (MA(III)), monomethylarsenous acid (MA(V)), dimethylarsenic acid (DMA(III)) and dimethylarsenous acid (DMA(V)) was not successful. However, separation of arsenic- -glutathione complexes - arsenic triglutathione (ATG), methylarsenic diglutathione (MADG) and dimethylarsenic glutathione (DMAG) was obtained. Several chromatographic peaks were observed at higher concentration of acetonitrile in mobile phase. The analysis of two in vitro methylation mixtures was also examined. Mixtures contained arsenite (As(III)), S-(5'-adenosyl)methionine chloride (SAM), tris(2-carboxyethyl)phosphine (TCEP) and arsenic(3+)methyltrasferase enzyme (AS3MT) probably participating in human arsenic metabolism. Second mixture also included glutathione (GSH). Several chromatographic peaks of complex species were obtained by analyzing these...
|
guest ::
