Toxicology (from the Greek words toxicon and logos) is the study of the adverse effects of chemicals on living organisms. It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people. The chief criterion regarding the toxicity of a chemical is the dose, i.e. the amount of exposure to the substance. Almost all substances are toxic under the right conditions. As Paracelsus, the father of modern toxicology said, “Sola dosis facit venenum” (only dose determines the poison). Paracelsus, who lived in the 16th century was the first person to explain the dose-response relationship of toxic substances.

Many substances regarded as poisons are toxic only indirectly. An example is "wood alcohol" or methanol, which is not poisonous itself, but is chemically converted to toxic formaldehyde and formic acid in the liver. Many drug molecules are made toxic in the liver, a good example being acetaminophen (paracetamol), especially in the presence of alcohol. The genetic variability of certain liver enzymes makes the toxicity of many compounds differ between one individual and the next. Because demands placed on one liver enzyme can induce activity in another, many molecules become toxic only in combination with others. A family of activities that engages many toxicologists includes identifying which liver enzymes convert a molecule into a poison, what are the toxic products of the conversion and under what conditions and in which individuals this conversion takes place.

The term LD50 refers to the dose of a toxic substance that kills 50 percent of a test population (typically rats or other surrogates when the test concerns human toxicity). LD50 estimations in animals became obsolete in 1991 and are no longer required for regulatory submissions as a part of pre-clinical development package.

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Human & Experimental Toxicology current issue

Acrylamide-induced oxidative stress in human erythrocytes
Catalgol, B., Ozhan, G., Alpertunga, B.Acrylamide (AA), a widely used industrial chemical, is shown to be neurotoxic, mutagenic and carcinogenic. This study was carried out to investigate the effects of different doses of AA on lipid peroxidation (LPO), haemolysis, methaemoglobin (MetHb) and antioxidant system in human erythrocytes in vitro. Erythrocyte solutions were incubated with 0.10, 0.25, 0.50 and 1.00 mM of AA at 37°C for 1 hour. At the end of the incubation, malondialdehyde (MDA), an end product of LPO, was determined by liquid chromatography (LC) while total glutathione, reduced glutathione (GSH) levels, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) enzymes and the rates of haemolysis and MetHb were determined by spectrophotometric methods. All of the studied concentrations of AA increased MetHb formation and SOD activity, and induced MDA formation and haemolysis due to the destruction of erythrocyte cell membrane. AA caused a decrease in the activities of GSH-Px, CAT and GSH levels. However, these effects of AA were seen only at higher concentrations than AA intake estimated for populations in many countries. We suggest that LPO process may not be involved in the toxic effects of AA in low concentrations, although the present results showed that the studied concentrations of AA exert deteriorating effects on antioxidant enzyme activities, LPO process and haemolysis.
Safety of a novel galacto-oligosaccharide: Genotoxicity and repeated oral dose studies
Kobayashi, T., Yasutake, N., Uchida, K., Ohyama, W., Kaneko, K., Onoue, M.A series of safety tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by a two-step enzymatic process involving Sporobolomyces singularis and Kluyveromyces lactis. Bacterial reverse mutation and chromosomal aberration tests, with or without metabolic activation, were performed. These tests showed no mutagenesis in the Ames assay or in Escherichia coli WP2uvrA, and no chromosomal aberrations in cultured fibroblast cells from Chinese hamster lungs (CHL/IU). Micronuclei were not induced in the reticulocytes of mouse peripheral blood following oral administration of GOS. In a 90-day repeated oral dose toxicity study in rats, GOS was administered at 0, 500, 1000 and 2000 mg/kg to male and female Sprague-Dawley rats. There were no GOS-related changes in clinical signs, body weight, water intake, feed intake, urinalysis, ophthalmology, haematology, blood chemistry, organ weights, gross pathology or histopathology in any of the treatment groups compared to the control group. The no observed adverse effect level (NOAEL) of GOS was at least 2000 mg/kg/day in both males and females.
Cardiac biomarkers in a model of acute catecholamine cardiotoxicity
Mladenka, P., Hrdina, R., Bobrovova, Z., Semecky, V., Vavrova, J., Holeckova, M., Palicka, V., Mazurova, Y., Nachtigal, P.Coronary heart disease and in particular its most serious form — acute myocardial infarction (AMI) — represents the most common cause of mortality in developed countries. Better prognosis may be achieved by understanding the etiopathogenetic mechanisms of AMI. Therefore, a catecholamine model of myocardial injury, which has appeared to be very similar to AMI in human in some aspect, was used. Male Wistar:Han rats were randomly divided into two groups: control group (saline) and isoprenaline group (ISO; synthetic catecholamine, 100 mg.kg— 1 subcutaneously [s.c.]). After 24 hours, functional parameters were measured, biochemical markers in the blood and metals content in the heart tissue were analysed and histological examination was performed. ISO caused marked myocardial injury that was associated with myocardial calcium overload. Close correlation between myocardial impairment (i.e. serum TnT, stroke volume index and wet ventricles weight) and the levels of myocardial calcium was observed. Direct reactive oxygen species (ROS) involvement was documented only by non-significant increase in malonyldialdehyde 24 hours after ISO injury. Moreover, myocardial element analysis revealed no significant changes as for the content of zinc and iron while selenium and copper increased in the ISO group although it reached statistical significance only for the latter.

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