ADME/TK Assessments
Our work
Central to the understanding of a substance’s toxicity is a consideration of its Absorption, Distribution, Metabolism and Excretion (ADME). How efficiently is a substance absorbed by the human body? How is it broken down? Which tissues does it reach and is it likely to bioaccumulate? How does the body eliminate the substance? All this comes under the general heading of toxicokinetics (TK). Generating new TK data in the laboratory involves the use of animals, is time-consuming and extremely costly (particularly if radiolabels are required). However, bibra specialises in making expert predictions, interpreting ADME assays, and taking into account what is already known about the toxicity of a chemical, its structure, and its physico-chemical properties.
Relevant properties for absorption (and other TK) assessment
In Silico
As well as using physico-chemical properties to predict TK properties, we make use of (Quantitative) Structure-Activity Relationships ((Q)SAR) modelling and software. The US EPA’s EPISuite tool allows physico-chemical properties to be predicted for compounds where experimental data are lacking. There are several “profilers” in the OECD (Q)SAR Toolbox that predict metabolic breakdown products; we have an expert partner who can conduct a similar analysis using the Meteor Nexus software.
TK Assessment under REACH
Conducting new toxicokinetic testing is not a requirement in the EU under the REACH regulation, but above 10 tonnes per year it is necessary to provide an assessment of the existing data. Understanding the toxicokinetic properties of a substance is very useful in determining the most appropriate route of exposure for future testing, likely target organs, and bioaccumulation potential, and in informing on the hazard and risk assessment (e.g. absorption values to be used in DNEL calculations).
Some of our case studies in this area
NAMs for NGRAs
Blog articles
Traditionally, toxicological risk assessment has involved identifying a point of departure (PoD) such as a NOAEL or LOAEL in a study of small creatures, adjusting it to be relevant to humans (to derive, for example, a TI or DNEL), and then calculating the margin of safety to a measured or estimated external exposure. As part of this process, toxicologists have to account for the uncertainties that arise in moving from the species, route and duration of the laboratory animal study to the real human world.
FDA memoranda: genotoxicity and carcinogenicity assessments of ENDS
Blog articles
As discussed in a previous blog post, the U.S. Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has issued several “scientific policy memoranda” that provide some great insights into the Agency’s evaluation process. In June 2024, the FDA made two new memos available that relate to the genotoxicity and carcinogenicity assessment of chemical constituents of Electronic Nicotine Delivery Systems (ENDS).
FDA memoranda: shedding light on health risk assessment of ENDS in PMTA submissions
Blog articles
In 2016, the United States (US) Food and Drug Administration (FDA) ruled that Electronic Nicotine Delivery Systems (ENDS) were to be regulated just like more traditional tobacco products, meaning that ENDS (e-cigarettes and e-liquids) are subject to premarket review requirements, despite containing no tobacco. ENDS manufacturers must therefore submit a Premarket Tobacco Product Application (PMTA) to the FDA Center for Tobacco Products (CTP) in order to have any chance of legally marketing their products in the US.
Some industries we work in
REACH
We are a leading supplier of REACH compliance services, assisting chemical manufacturers, importers and downstream users comply with their REACH Regulation responsibilities.
Medical Devices
We are adept at conducting biocompatibility assessments and biological safety evaluations of medical devices in compliance with ISO 10993, FDA and European guidelines, to help bring your device to market.
Pharmaceuticals
Our team is adept at preparing critical toxicological reports - we regularly provide assessments of novel or unexpected impurities, excipients and other intentionally-added substances, and extractables and leachables.
