At the Bleeding Edge: Benchmarking Next-Gen NanoTox Protocols


                        Image: "Old-school" ZnO. Source: U.S. National Library of Medicine of the National Institutes of Health





FIND At the Bleeding Edge: Benchmarking Next-Gen NanoTox Protocols LISTED UNDER: RESEARCH METHODOLOGIES AND TOOLS   



For all of the razzmatazz accorded Tox21's recent implementation of a state-of-the-art robotic system at NIH's Chemical Genomics Center, it advances by not one nanometre the sorry state-of-the-science sustained by nanotoxicology research and contributes negligibly to the elucidation of the infinitely more complex interactions of manufactured nanoforms and the diversification of emergent nanophysiological dynamics that can give rise to nanotoxicity.

While comprehension of molecular composition has been fundamental to standard, established hazard evaluations, risk assessments, and regulations-setting, the NIEHS ToxCast High-Throughput Screening Initiative's orientations towards basic chemical composition conventions and comparatively simplistic substance behavioural observations elude the urgent challenge of highly-refined, relevant fate and exposure explorations into engineered nano-scaled materials according to their specific potential toxicological synergies and structures and their peculiar emergent properties, processes, and patterns.

Proposed here are considerations for optimization of the National Toxicology Program's Nanotechnology Safety Initiative and its NanoHealth Enterprise Framework to move meaningfully and measurably forward towards structure and device standardization while keeping pace with state-of- knowledge advances during the 5-years' Strategy Plan period and beyond.

               Image: "Next-Gen" Nanocellulose   Source: Wikimedia


1. Devise a discrete predictive system by creating NEW PREDICTIVE PROTOTYPE that integrates 3D-QSAR/QSPR modelling, ex vivo procedures, virtual compound screening methodologies, and 3D- Pharmacore mapping with a view towards scaling out and up to PBPK-type modelling. Tightly-tweak well-defined nanomaterials domain descriptors to increase hit-rates and design new assays [as per Burello and Worth].

Design particle-specific delineations according to morbid, mortal, latent, lethal, desirable, and deleterious, acute, chronic, naturally-occurring, and fabricated exposure toxicity differentials. Link NPC characterizations to toxic causality identifications (above) and incorporate into progressively predictive QSAR/PBPK prototype system. Improve testing correlations, cross-species outcomes. Influence safety-by-design mandates based on particle-protein specifications and nano-component locale. Focus on corona compartmentalization
[as per Faunce, White, and Matthaei] to minimize/eliminate toxicity and to reduce the cacophony of confusion on the matter.
 The corona is where defect, deformation, dysfunction, disruption, disease, and death will more readily reveal themselves.

3. Make revolutionary NANOMETROLOGY the sine qua non.


4. Move ever forward towards a TRULY TRANSLATIONAL approach.

5. Set the standard for toxic torts- and then RAISE IT; none of which will happen without a dedicated NANOINFORMATICS unit devoted strictly to the NTP. 


6. REFUSE to fail upwards. RENDER UNTO THE SCRAP  HEAP all UNWORTHY, UNWORKABLE, UNSCALABLE projects. RETURN that REVENUE and those resources to permanent nanotox research line item status.



[DISCLOSURE STATEMENT: The author of this blog post is CKO of Plutonic Research & Knowledge Teams Intl [PRAKTI] and directs its DeepMed library division. The blogger has no other relevant affiliations, competing interests, or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter, materials, products, or agencies discussed. The blogger is the sole author of this entry].  



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Tags: NIEHS, NPC, NTP, Pharmacore, QSAR, computational_nanotoxicology, ecotoxicity, in_silico, nanoinformatics, nanomedicine, More…nanometrology, nanoparticle-protein_corona, nanosafety, nanotoxicology, protocols, systems_biology


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