General thoughts, comments, questions on nanomaterial characterization for toxicology studies, MINChar, the website, the community, the parameters list, and anything else that seems relevant.

If you have specific questions that you would like to open up for discusison, post them here and we will open a new conversation thread.

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5 Responses to “General Comments Dec 08”

  1. Vicki Stone Says:

    Investigating the relationship between the physicochemical chemical characteristics of nanoparticles and their behaviour in biological systems will be essential to understand toxicity and to predict risk. At this time there is pressure on toxicologists to ensure that their nanoparticle is characterised before use, on exposure to their model system and throughout the incubation period. I would like to raise several issues that relate to this:
    Firstly characterisation in biological media is very difficult and therefore not yet truely achievable.
    Secondly it is very costly to conduct this level of characterisation.
    Thirdly, is this level of characterisation really necessary? For other toxic particles (e.g. silica and asbestos) characterisation of the pure material has allowed identification of the characteristics that drive toxicity.
    An understanding of how nanoparticles behave in biological systems will help us to understand why they are toxic, but is this the same as a full characterisation of their physicochemical characteristics at every step of the study?

  2. Andrew Maynard Says:

    Thanks Vicki.

    I think these are important points.

    I would be very interested in hearing what others have to say on the degree to which poor characterization has limited the interpretation and use of nanotox studies to date, and whether useful knowledge can be generated for some materials with a more limited understanding of physicochemical characteristics than is recommended here.

  3. Fred Klaessig Says:

    Dear Andrew and Professor Stone,

    Let me start with best wishes for the New Year, a good Hogmanay and, as my German colleagues would say, “einen guten Rutsch ins neue Jahr.”

    Professor Stone’s question is one that we all ask, “when is enough, enough?”, especially when one scientific discipline is doing the work normally associated with a second discipline. The authors of the literature articles we discussed in Washington, those with with zero data, or supplier name plus zero data, or minor, somewhat inexplicable characterization data, they were not shy when speculating about the implications of their work. These speculations, in turn, created work for others in pursuing issues that range from the truly substantive to time-wasting distractions. In some respects, the proper division of labor between scientific disciplines is being discussed under the headline of the scientific quality of an individual paper.

    In Washington, there appeared to be a consensus on obtaining particle characterization on an “as administered” basis, with further study in biological fluids being dependent on the investigator’s dominant hypothesis. We were less certain about commenting on speculations, which is why the Clancy Score targeted audiences that are editorial boards, funding agency reviewers, i.e. those who have the professional background in setting the balance between an article’s overall scientific quality and its timeliness.

    Perhaps, though, we are dwelling on the negatives (some may remember the tune, “accept the positive, eliminate the negative, latch on to the affirmative, don’t mess with Mister In-Between). Measuring and reporting particle size distribution data (PSD) for TiO2 has led to progress in preparing stock suspensions. The steps I note are:

    (1) Warheit et alia in 2007 reports provide PSD data for TiO2 in water (~130 nm) and PBS (>2000 nm), but no effect on SiO2;
    (2) Sager et alia in 2007 confirmed these observations, noting, too, that Carbon Black behaves similarly to TiO2 in terms of PSD. In her thesis, Sager used BALF as an alternative suspending agent and observed a greater biological response for TiO2 when it is dispersed to a smaller particle size;
    (3) Castranova et alia in 2008 proposed an alternative dispersion protocol using species-specific Serum Albumin and DPPC as particle dispersants in a Ca++ and Mg++ free PBS;
    (4) Bihari et alia in 2008 examined multiple dispersion protocols for 11 materials leading to a preference for PBS + HSA. All of the materials exhibit similar zeta potentials when dispersed in the recommended manner, an observation that might point to a quantifiable end point when deciding on how much dispersant is needed in the PBS suspension.

    Essentially, we have here a worthy progression of articles where the investigators are clarifying the issues surrounding dispersion protocols, including the possibility of protocol-driven artifacts, when preparing stock suspensions. This would not have been possible if David Warheit and others had not started the process by reporting on particle characterization data in the “as administered” suspension.

    Yours,

    Fred

  4. Shaun Clancy Says:

    Greetings to all,

    I’d like to provide my thoughts on the three concerns Vicki has raised. I can imagine that her points could have been raised by many others.

    >>>>Firstly characterisation in biological media is very difficult and therefore not yet truly achievable.

    ****The characterization elements recommended in the Community’s Parameter List are fairly routine, to the best of my knowledge. Using these methods in actual biological settings may be challenging but synthetic biological fluids may be suitable surrogate conditions.

    >>>>Secondly it is very costly to conduct this level of characterisation.

    ****I believe the greatest part of the costs is to obtain and install equipment. But this has already been done in many characterization labs. Rather than looking at the need for characterization as a barrier I look at it as an opportunity for increased collaboration between toxicologists and physical chemists/materials scientists. Toxicologists should not have to become P-Chemists and vice-versa.

    >>>>Thirdly, is this level of characterisation really necessary? For other toxic particles (e.g. silica and asbestos) characterisation of the pure material has allowed identification of the characteristics that drive toxicity.
    An understanding of how nanoparticles behave in biological systems will help us to understand why they are toxic, but is this the same as a full characterisation of their physicochemical characteristics at every step of the study?

    ****I believe this level of characterization is essential. I believe that the concept of “nano-toxicology” is based on a concern that particle sizes in the nanoscale may introduce new hazards not seen in larger forms of the same chemical substance. If this is true then it is very important for a material to be sufficiently characterized so that if a biological response is attributed to the particle size of a material that the reported size is accurate in the medium in which the test(s) were performed.

  5. Anil Patri Says:

    I’d like to bring up the sterility and endotoxin contamination issues for discussion. We pre-screen all nanomaterial routinely and do not proceed with biological testing if the samples are contaminated or beyond acceptable limits for endotoxin. Nanomaterial interefere with standard (LAL) assays and the inhibition and enhancement controls fail in many cases. While this may seem to be obvious and trivial for a biologist, we feel it necessary to test each sample for contamination and recommend this as a good practice.

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