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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Adverse effects of lactational exposure to chlorpyrifos in suckling rats
Mansour, S., Mossa, A.The present study was undertaken to evaluate the oxidative damage, biochemical and histopathological alterations in sucking rats whose mothers were exposed to the insecticide chlorpyrifos (CPF). Dams were administered CPF, via oral route. Doses equalled 0.01 mg kg—1 body weight (b.wt.; acceptable daily intake, ADI), 1.00 mg kg—1 b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg—1 b.wt. (1/100 lethal dose [LD50]) from postnatal day 1 until day 20 after delivery. At two high doses of CPF, the body weight gain and relative liver and kidney weight of suckling pups were significantly decreased. Exposure of the mothers to CPF caused increase in lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD) and glutathione-s-transferase (GST) in lactating pups. CPF altered the level of the marker parameters related to the liver and kidneys. Consistent histological changes were found in the liver and kidneys of the subjected pups, especially at the higher doses. The results suggested that the transfer of CPF intoxication through the mother’s milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. The data of this study may be considered as a contribution to the problem of lactational transfer of the relatively less persistent OP pesticides, such as CPF.
Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity in rats
El-Bakary, A. A, El-Dakrory, S. A, Attalla, S. M, Hasanein, N. A, Malek, H. AMethanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.
L-Ascorbate protects rat hepatocytes against sodium arsenite--induced cytotoxicity and oxidative damage
Asit Kumar Bera, , Rana, T., Das, S., Bandyopadhyay, S., Bhattacharya, D., Pan, D., De, S., Subrata Kumar Das, Sodium arsenite—exposed hepatocytes of rat showed higher production of nitric oxide (NO) and increased lipid peroxidation (LPO) level vis-a-vis activity of superoxide dismutase (SOD) and catalase (CAT) were significantly lowered. Subsequently, the cell proliferation index (CPI) and cell viability were also reduced. Treatment with L-ascorbate was found effective in normalizing the arsenic-induced alteration of SOD and CAT activity and LPO level in rat hepatocytes. These observations indicated that L-ascorbate also has potent cytoprotective role as it could reduce the NO production and normalize the cell proliferation and viability of hepatocytes. Therefore, the in vitro study suggested that ascorbic acid is helpful to ameliorate the arsenic-induced cytotoxicity and oxidative stress of rat hepatocytes.

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