Nanotoxicology & Respiratory Toxicology

CXR can compare likely toxicological risk across research compounds/formulations, assist in the better design of formal safety studies, and assess relevance to man of previous adverse findings.

Nanotechnology can be defined as the manipulation, precision placement, measurement, modeling, or manufacture of sub-100 nanometer scale matter. Nanoparticles are increasingly used in a range of industries, including engineering, environmental technology, information technology, food, health, chemicals and agrochemicals, and pharmaceuticals. With increased use, there is recognition that nanoparticles can display unexpected toxicology and require testing on a case by case basis to address potential risk.

Adverse effects can manifest via a range of actions (particularly oxidative stress) and in a number of organs, ranging from respiratory and cardiovascular (diesel exhaust or bulk manufacture) and gut (food additives) to systemic and hepatic (drug delivery/carrier systems and novel imaging modalities). An appropriate battery of in vitro and in vivo testing will be required to assess systemic toxicology as well as tissue specific adverse effects (e.g. respiratory, cardiovascular, dermal and hepatic).

The situation for developers of nanomaterials is complicated by the evolving status of regulatory guidance. Until recently, there was very little specific guidance for nanoparticles, but this is changing in both the chemical and pharmaceutical industries:

Recently there has been concern that the current registration threshold limit of 1 tonne under REACH may not be suitable for nanomaterials and there is the suggestion that nanoscale substances < 1 tonne per year should be registered. This is an approach which has now been taken by the French whom in February 2012 published a decree that all companies producing, distributing or importing nanomaterials in France irrespective of quantity, must register this by July 2013.

In 2011, the EMA published a “Reflection paper on non-clinical studies for generic nanoparticle iron medicinal product applications.” Amongst other conclusions it stated that, when assessing a nanomedicine, assessing tissue concentrations (not just plasma PK) is required, as concentrations can differ depending on nanoparticle characteristics.

As regulatory concerns grow and develop for the nanotechnology industry, CXR has developed a broad platform of in vitro and in vivo models for designing and conducting early investigative and mechanistic safety assessment programmes, which can be used to compare likely toxicological risk across research compounds/formulations, assist in the better design of formal safety studies, and assess relevance to man of previous adverse findings.

CXR can help you:

  • Interpret regulatory guidance
  • Design mechanistic safety studies and programmes, for instance to assess likely toxicological hazard and risk across research compounds / formulations
  • Elucidate the mode of action of nanoparticle and respiratory toxicology and assess relevance to man

CXR Biosciences services offering:

Nanoparticle characterisation:

  • Size
  • Surface area
  • Charge
  • Composition
  • SEM/TEM

In vitro models of nanotoxicology and respiratory toxicology:

  • Cell culture (e.g. respiratory, cardiovascular, immune, dermal, hepatic)
  • Toxicity (e.g. mitochondrial dysfunction, membrane damage)
  • Oxidative stress
  • Inflammation
  • RT-PCR, Western Blot analysis, Microarray, Bioinformatics

In vivo models of nanotoxicology and respiratory toxicology:

  • Rodent intra-tracheal, intra-pleural and pharyngeal aspiration routes of delivery in both wild-type and transgenic animals
  • Toxicity, PK/PD
  • Assessment of tissue inflammation and fibrosis
  • Clinical chemistry and haematological measurements
  • Histology and Immunocytochemistry
  • RT-PCR, Western Blot analysis, Microarray, Bioinformatics

For further information about our services, or to discuss a specific issue, please contact us.

Download the Nanotoxicology & Respiratory Toxicology brochure here

The Use Of An Oxidative Stress Associated in vitro Screen For The Prediction Of Potential Nanoparticle Toxicity. The poster was presented at Nanomedicine 2013.