Central to the understanding of a substance’s toxicity is the consideration of its toxicokinetics. How efficiently is a substance absorbed by the human body? How is it broken down, and which tissues does it reach? Is it likely to bioaccumulate? How does the body eliminate the substance? Generating toxicokinetic data in the laboratory involves the use of animals, is time consuming and extremely costly (particularly if it involves the use of radioactive isotopes). It is possible, however, by taking into account existing knowledge of the toxicity of a chemical, its structure and its physico-chemical properties, to make certain predictions. However, expert knowledge is a prerequisite for accurate interpretation.
Several properties can impact on the toxicokinetics of a substance, including:
- Physical form – solid, liquid or gas?
- Molecular weight/size
- Water solubility
- Vapour pressure
- Partition coefficient (Log Kow)
There are a number of ways in which our team of experienced toxicologists can help you. We can conduct extensive literature searching for existing data on the toxicokinetics of a substance (or of related chemicals). In the absence of specific toxicokinetic data, we could look for information on the target tissues of a compound and the relative toxicity via different routes (e.g. oral, inhalation, dermal), species (e.g. rodent and man) and between the sexes. We also have experience in analysis of chemical structure and physical-chemical properties, from which we can predict the likely behaviour of a molecule.
Conducting new toxicokinetic testing is not a requirement in the EU under the REACH regulation, but an assessment of the toxicokinetic properties of a substance is very useful in determining the most appropriate route of exposure for future testing, likely target organs, bioaccumulation, and in informing in the hazard and risk assessment (e.g. % absorption values to be used in DNEL calculations). For an example, please see information on our on going work for the Precious Metals Consortium. The use of vertebrates is also banned for cosmetics testing in the EU, so a desk-based TK assessment can be invaluable. Bibra can assess all of the relevant information to produce an evaluation that meets the requirements of the regulators, and satisfies the data needs of the hazard and risk assessor.
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