IN SILICO CONSULTING

Our experts offer expert advice based on our in-house software iSafeRat® and dozens of quality third party software packages to predict toxicology, ecotoxicology and physical chemistry endpoints for all kinds of regulatory and R&D needs. We prepare consensus outputs to judge the intrinsic properties of chemicals including potential for CMR, PBT/PMT and Endocrine disruption.

The quality of in silico predictions has advanced by leaps and bounds over the last decade. Today, between our own home-grown iSafeRat® Toolbox values and those of third-party software, it is possible to completely fulfil your regulatory needs using nothing but in silico data for ecotoxicology and human health assessments* saving you months of work and reducing the cost of your dossier by a factor of 5.

Using in silico models, we can propose quality toxicity predictions for, “CMR” (Carcinogenicity, Mutagenicity, Reprotoxicity) and sensitisation (often including the EC3 calculation) which are recognised as primary human health hazards for screening of substances. We also offer eye and dermal irritation/corrosion, dermal absorption, oral LD50, and repeated dose toxicity using a read-across approach identifying NOAELs from analogue substances. For environment we offer “PBT/PMT” (Persistent, Bioaccumulable, Toxic or Persistent, Mobile, Toxic) substance profiling and detailed ecotoxicolgical information using the KREATiS MechoA (Mechanisms of Toxic Action) scheme, which is now also included as a profiler in the world renowned OECD QSAR Toolbox.

In all cases the target substance must be within the applicability domain of the models and a full regulatory format is required to demonstrate this. Our experts can guide you to the most appropriate solution.

*It is recognised that not all countries or regulatory frameworks accept all in silico alternatives to testing at this time, but the list of accepted replacements is growing and new AI breakthroughs are being made all the time. For example, Korea has recently decreed that in silico data can be used in regulatory submissions of chemicals up to 10 TPA.

REACH

New substance registrations and dossier updates can be carried out with a host of in silico methods from specific High Accuracy QSARs from iSafeRat® Toolbox completed with full regulatory formats (QMRF and QPRF) to read-across strategy using data from other existing, similar structures, all reducing the need for performing long and expensive studies.

Moreover, iSafeRat® Toolbox contains a mixture toxicity module which accurately calculates the equivalent of a WAF (Water accommodated Fraction) value for multi-constituent substances.

Pharmaceuticals

The ICH M7 guideline provides a framework in order to assess and verify DNA reactive impurities in pharmaceutical products.

The results from two complementary QSAR methodologies, one expert rule-based and one statistical-based, are used together to support an initial hazard classification and reduce the number of required experimental in vitro studies. KREATiS has licences to use both methods.

Cosmetics

Testing on vertebrate animals is no longer accepted in the EU for the safety assessment of cosmetic products and their ingredients. Both industry and regulators worldwide recognise the invaluable information being provided by in silico methods as an alternative to testing chemical toxicity in vertebrate animals.

Plant Protection Products and Biocides

The importance of in silico predictions, even for bioactive substances, should not be underestimated. Such substances are often accompanied by impurities or are metabolised or biodegraded into multiple other structures which may be difficult to synthesise or to test and for which computational (eco)toxicology is a simple and rapid solution.

Look at the apps we use