Hazard Characterisation
Hazard Characterisation
Our hazard assessments, generally based on in-depth searches of the scientific literature, aim to define the dose-response for all routes of each of a chemical’s toxicological propensities, for example its carcinogenicity, genotoxicity, or ability to disrupt reproduction.
We summarise all of the available data in a transparent format, taking into account the needs of our clients – for example, if there is a specific structure or format required to comply with a particular regulation.
As experienced risk assessors ourselves we are well placed to ensure that our hazard characterisation – the potential to induce a harm - provides the best possible platform the available data (and budget) will allow for any subsequent risk assessment, a judgement as to whether those harms will actually be seen in a specific circumstance.
Routes of Administration
Screening assessments
Often, we are asked to assess several compounds that could be of potential health risk to a patient. We have developed a “screening” process where we can prioritise those substances that are more likely to result in a health risk. Compounds present at very low levels, or without inherent toxic hazards, can, with appropriate justification, be excluded from further more detailed and expensive toxicological risk assessment.
(Q)SAR
More and more computational models are being developed to link a particular toxicological hazard with a chemical structure. This is called (Quantitative) Structure-Activity Relationship ((Q)SAR) modelling. When we are faced with a data-poor chemical, we routinely use (Q)SAR to generate predictions and identify possible areas of concern, or endpoints worthy of further investigation. Even the most sophisticated models still currently require a sanity check and bibra’s experienced toxicologists are ideally placed to provide it.
Safety Benchmarks
Often, a toxicological hazard characterisation is the major first step on a pathway leading to a health-based guidance value. Such a value is an estimate of the maximum exposure, generally qualified by route (parenteral, inhalation, oral or dermal), that will pose no significant threat to human health. It will usually be based on data from laboratory animal experiments, adjusted to account for the likely differences in how humans and the other species (usually a rodent) is likely to respond to chemicals in general or (much more rarely) to that specific test chemical.
Some industries we work in
Nicotine Products
We provide valuable advice on toxicological issues relating to e-cigarettes (and other nicotine delivery devices), and can support your regulatory submissions within the scope of EU TPD, UK TRPR and the US FDA PMTA.
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.
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.
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.
