Case Studies

CASE STUDIES

Methodology applicability and real life use case.

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DOSE RESPONSE – composite dust

AT WHICH DOSE THE DUST FROM CARBON FIBER COMPOSITE BECOMES LONG-TERM HAZARDOUS?​

  • In finite platform delivers long-term safety dose assessment in just 4 days
  • In finite platform relies on the automated discovery of Mode-of-Action instead on preexisting knowledge on toxicants and predetermined toxicological thresholds
  • 3 dust sites from carbon fiber composite processing sampled in this case
  • All samples trigger acute inflammation above air concentrations of 0.8 – 4 mg/m3, but only one triggers weak long-term inflammation at very high air concentrations above 2.3 mg/m3.

WORKPLACE SAFETY – clay materials

WHICH WORKING PLACE (AMONGST TESTED IN OUR DUSTY INDUSTRIAL ENVIRONMENT) IS THE MOST LONG-TERM HAZARDOUS?

  • In finite platform delivers long-term safety assessment in just 4 days
  • In finite platform relies on the automated discovery of Mode-of-Action instead on preexisting knowledge on toxicants and predetermined toxicological thresholds
  • 3 sites along clay processing line sampled in this case
  • All samples trigger acute inflammation at surface doses above 0.3:1 that resolves in 3 months; one sample triggers also strong subacute inflammation, none triggers chronic inflammation.

FUNCIONALIZATION – nanomaterial

DOES THE FUNCTIONALIZATION OF A NANOMATERIAL SURFACE CHANGE ITS SAFETY?

  • In finite platform delivers long-term safety assessment in just 4 days.
  • In finite platform relies on the automated discovery of Mode-of-Action instead on preexisting knowledge on toxicants and predetermined toxicological thresholds
  •  2 engineered nanomaterials with different types of surface functionalization, either with carboxyl or hydroxyl functional groups, were sampled in this case
  • Both samples trigger acute inflammation at surface doses above 0.3:1 or 0.5:1; in one case, inflammation is resolved in less than a week, while in other case persists for almost 3 months as a strong subacute and subchronic inflammation; none triggers chronic inflammation.

PHYSICAL PROCESSING

CAN THERMAL PROCESSING MAKE NON-HAZARDOUS STARTING TiO2 ANATASE LONG-TERM HAZARDOUS?

  • In vitro assays, targeting specific endpoints within the inflammatory response, face limitations in capturing the intricate dynamics of in vivo processes and lack consistency in predicting outcomes, especially in the proximal and small airways
  • In vivo assessments, while more comprehensive, are extremely time-consuming, costly, and may not consistently translate to human-relevant outcomes
  • By integrating in vitro experiments and in silico modeling, In finite system learns complex interactions between cells and tested materials, thereby deriving their mode-of-action (MoA) and prediction of chronic inflammation in a matter of days, offering unprecedented timeline for hazard assessment and mitigation.

ADVERSE DRUG REACTIONS

WHAT SECONDARY PROCESSES ARE TRIGGERED BY OUR COUMPOUND?

  • Adverse drug reactions (ADRs) impose significant economic and clinical challenges, contributing to 11% of global hospital admissions
  • Randomized controlled trials (RCT), the gold standard for evaluating efficacy, struggle to detect long-term ADRs
  • RCTs are very expensive, with US costs alone estimated at 30.1 billion US2 – “Reducing the costs of trials is absolutely crucial for the public good”
  • In finite platform delivers ADR evaluation in 1 week
  • In this study, In finite platform identified several side effects of a test drug, including its reduction of lipid production, synaptogenesis and potential neurotoxicity.

DRUG DISCOVERY

PRECLINICAL IDENTIFICATION OF POTENTIAL DRUG CANDIDATES FOR ALZHEIMER'S DISEASE

  • Alzheimer’s drug development spans decades and costs billions, with the preclinical phase consuming up to 40.5% of total expenses1,2, stemming from the usage of transgenic animal models despite the fact 99% of cases are environmentally driven
  • The translational success of potential drugs from preclinical to clinical phases is additionally hindered by the significant mismatch between animal models and human pathology
  • In finite relies on mode-of-action (MoA) based long-term neurodegeneration prediction in few days without genetic manipulations for only a fraction of a cost
  • 4 out of 20 tested substances exhibited a notable reduction in damage and restoration of communication disrupted by extracellular plaques and axonal loss
  • Amongst these, In finite platform predicts that treatment with 100 nM Compound 13 potentially prevents neurodegeneration development.

CANCER RISK SAFETY

WHICH CARBONACEOUS PARTICULATES ARE SAFER REGARDING POTENTIAL CANCER RISK?

  • Standard animal carcinogenicity studies are enormously long and costly
  • In finite assessment delivers long-term safety assessment in just 4 days
  • In finite platform relies on the automated discovery of Mode-of-Action, here focused on chronic inflammatory potential, aneuploidy, and other intracellular damages that, in combination, lead to the development of cancer
  • 4 combustion engines are assessed here by identifying their potential of triggering chronic inflammation and increased risk of lung cancer.
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