Toxicokinetics
Little Pro on 2016-04-26
Toxicokinetics(TK) is essentially the study of how a substance gets into the body and what happens to it in the body. Studies examining the toxicokinetics (TK) of a chemical substance are conducted to obtain adequate information on its absorption, distribution, biotransformation (i.e. metabolism) and excretion, to aid in relating concentration or dose to the observed toxicity, and to aid in understanding its mechanism of toxicity. TK data can also contribute to the assessment of the adequacy and relevance of animal toxicity data for extrapolation to human hazard and/or risk assessment.
All 4 processes( absorption, distribution, metabolism and excretion) are essential for understanding the systematic toxicity of a chemical substance.
Absorption
The ability to be absorbed is essential for systemic toxicity to occur. Some chemicals are readily absorbed and others poorly absorbed. For example, nearly all alcohols are readily absorbed when ingested, whereas there is virtually no absorption for most polymers.
The key factor in the quantitative assessment of human health risk from chemical exposure is the correct quantification of the amount of the chemical substance passing through the bio-membrane(i.e,skin) and thus actually entering the body. Without the TK study, usually 100% absorption is assumed, which may over-predict the risks of systematic toxicity.
Metabolism
Metabolism, also known as biotransformation, is a major factor in determining toxicity. The products of metabolism are known as metabolites. There are two types of metabolism - detoxification and bioactivation.
- Detoxification is the process by which a xenobiotic is converted to a less toxic form. This is a natural defense mechanism of the organism. Generally the detoxification process converts lipid-soluble compounds to polar compounds.
- Bioactivation is the process by which a xenobiotic may be converted to more reactive or toxic forms.
Distribution
The distribution of toxicants and toxic metabolites throughout the body ultimately determines the sites where toxicity occurs. A major determinant of whether or not a toxicant will damage cells is its lipid solubility. If a toxicant is lipid-soluble it readily penetrates cell membranes. Many toxicants are stored in the body. Fat tissue, liver, kidney, and bone are the most common storage depots. Blood serves as the main avenue for distribution. Lymph also distributes some materials.
Excretion
The site and rate of excretion is another major factor affecting the toxicity of a substance. The kidney is the primary excretory organ, followed by the gastrointestinal tract, and the lungs (for gases). Substances and metabolites may also be excreted in sweat, tears, and milk. A large volume of blood serum is filtered through the kidney. Lipid-soluble toxicants are reabsorbed and concentrated in kidney cells. Impaired kidney function causes slower elimination of toxicants and increases their toxic potential.
Testing Guidelines
- Toxicokinetics (OECD TG 417)
- Species: Rat
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Congratulations! You have learned the definition of toxicokinetics, and why the information on absorption, distribution, metabolism (bio-transformation) and excretion is important for understanding the systematic toxicity of a substance and human health risk assessment. |
Continue Learning...
- Acute toxicity (oral, inhalation, dermal)
- Skin and eye irritation
- Sensitization (skin, respiratory)
- Repeated dose toxicity (28d, 90d and chronic)
- Mutagenicity and genotoxicity
- Reproductive and developmental toxicity
- Carcinogenicity
- Toxicokinetics
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