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.

More on [ Toxicology ]

Human & Experimental Toxicology current issue

The significance of serum levels of adiponectin, leptin, and hyaluronic acid in hepatocellular carcinoma of cirrhotic and noncirrhotic patients
Sadik, N. A. H., Ahmed, A., Ahmed, S. Tue, 01 May 2012 02:31:23 -0700
It is well established that hepatocellular carcinoma (HCC) develops in a multistep process, from chronic hepatitis, cirrhosis to HCC. Adipose tissue is not simply an energy storage organ but also a secretory organ, producing a variety of bioactive molecules known as adipokines, including adiponectin and leptin. Hyaluronic acid (HA) is an extracellular matrix protein, often associated with a variety of human cancers. Our retrospective study determines serum levels of adiponectin, leptin, and HA in HCC of cirrhotic and noncirrhotic patients and compares these levels to patients with cirrhosis and normal subjects. Noncirrhotic HCC (n = 19), cirrhotic HCC (n = 50), cirrhosis (n = 36) patients and twenty one age-, sex-, and body mass index (BMI)-matched normal healthy controls were subjected in the present study. Serum adiponectin, leptin, and HA levels were determined using enzyme-linked immunosorbent assay technique. Levels of serum adiponectin were significantly higher in the cirrhosis and cirrhotic HCC groups than in the normal subjects, whereas serum HA levels were found to significantly increase in all three patients groups. The elevation of serum leptin in our HCC patients, regardless of being cirrhotic or noncirrhotic, but not in the patients with cirrhosis, may shed some light on the significance of serum leptin level in HCC. Further studies are recommended to evaluate the prognostic value of serum leptin level in HCC.
Study on the cytogenetic changes induced by benzene and hydroquinone in human lymphocytes
Peng, D., Jiaxing, W., Chunhui, H., Weiyi, P., Xiaomin, W. Tue, 01 May 2012 02:31:23 -0700
Benzene (BN) is a prototypical hematotoxicant, genotoxic carcinogen, and ubiquitous environmental pollutant. Although the molecular mechanisms of BN-induced cytotoxicity and genotoxic damage are poorly understood in humans, previous studies suggested that bioactivated BN metabolites are capable of oxidative stress, cell cycle arrest, apoptosis, and DNA damage. The objective of the current study was to investigate the BN-induced cytogenetic changes and underlying mechanisms based on these hypotheses. Peripheral blood lymphocytes (PBLs) might be the targets for BN-induced cytotoxicity and genotoxicity, and therefore DNA damage responses of PBLs after exposure to different concentrations of BN (0.25, 3.5, 50 μmol/L) or BN metabolite, hydroquinone (HQ; 50, 150, 450 μmol/L) were studied in vitro. Microculture tetrazolium assay, flow cytometry, 2',7'-dichlorodihydrofluorescein-diacetate assay, comet assay, micronuclei assay, and attenuated total reflectance microspectroscope were chosen for this study. Based on the results, we reached the conclusion that different concentrations of BN or HQ significantly inhibited cell growth, induced the arrest of S phase and G2/M phase, and increased late apoptosis in a concentration-dependent manner. Furthermore, evidence was also provided to support the conclusion that BN and HQ induced DNA strand breaks and chromosomal mutations in PBL, which indicated the genotoxicity of BN and HQ. Current evidence has indicated that multiple mechanisms including dysfunction of cell cycle, programmed cell death, oxidative stress, and DNA lesions are likely to contribute to BN-induced cytogenetic changes.
Short-term exposure of 4-hydroxynonenal induces mitochondria-mediated apoptosis in PC12 cells
Siddiqui, M., Kumar, V., Kashyap, M., Agarwal, M., Singh, A., Khanna, V., Al-Khedhairy, A., Musarrat, J., Pant, A., Jahan, S. Tue, 01 May 2012 02:31:23 -0700
4-Hydroxynonenal (4-HNE) is one of the most reactive aldehydic by-products of lipid peroxidation. The role of 4-HNE in the etiology of various neurodegenerative disorders including cerebral ischemia/reperfusion, Alzheimer’s disease, Parkinson’s disease, etc. has been documented. We and others have reported that long-term toxic insults of 4-HNE triggers apoptotic signals and oxidative stress in various cells. However, the status of apoptosis following short-term exposure and underlying mechanisms has not been explored so far. We studied the apoptotic changes in PC12 cells receiving short-term exposure of 4-HNE. A significant dose-dependent induction in reactive oxygen species (ROS) and early response markers (c-Fos, c-Jun, and GAP-43) were observed in cells exposed to 4-HNE (10, 25, and 50 µM) for 1h. Following the exposure of PC12 cells to 4-HNE, the levels of protein and messenger RNA expressions of P53, Bax, and caspase 3 were significantly upregulated, whereas the levels of Bcl2 was downregulated. We could record the apoptotic signals and ROS generation in PC12 cells receiving 4-HNE exposure for such a short period of time. Induction in the expression and activity of caspase 3 has also indicated the mitochondrial mediation in the apoptosis induction.

Subscribe to Toxicology RSS feed