Science1 publisher2 min readPublished
OECD publishes guidance for tracking poorly soluble nanoparticles through the body
The OECD has published guidance on designing studies that track poorly soluble nanoparticles like titanium dioxide, which can linger in organs for months. It fills a gap in a 2010 test guideline written for dissolved chemicals that excludes nanomaterials.
The Scientist · Science desk
What happened
- The document, on toxicokinetics for testing nanoparticles, sets out how researchers should design, run and report studies of particles that are swallowed or inhaled.
- Two studies that injected identical 21-nanometer particles measured liver half-times of 95 and 265 days, and most feeding studies ran too short to calculate one at all.
- EFSA and France's ANSES both said in 2019 that data gaps, not proof of harm, meant earlier safety conclusions on titanium dioxide as a food additive could not be upheld.
- The guidance reviews radioactivation, which irradiates the particle so its own atoms can be followed, and rates it suitable for studies of up to 90 days.
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Why it matters
- constraint Because a poorly soluble particle can take months to years to leave an organ, a valid retention study has to follow animals far longer than the short feeding studies regulators previously relied on.
- decision Regulators who set aside earlier titanium dioxide conclusions in 2019 now have an agreed study design to fill the gaps that prompted them.
- precedent Internationally agreed test methods, previously scoped for dissolved chemicals, now extend to swallowed and inhaled nanoparticles.
A toxicokinetic study asks where a substance goes, how much builds up and how long it stays. For a chemical that dissolves, a series of blood samples answers most of it, and that is the design the OECD's 2010 test guideline was built around [2]. Poorly soluble nanoparticles break that design. Immune cells pull them out of the blood quickly, and they gather in a few organs, so a blood draw reads close to zero while those organs keep loading up [3].
Titanium dioxide shows why the gap matters for something people already eat. Used as a food additive, the white pigment is barely absorbed, no more than about 0.5% of a dose according to EFSA [7]. That sliver still turns up in human liver and spleen, and how fast it clears has been hard to establish [8].
The clearance rate is hard to pin down partly because the particles are hard to find. Studies of the three kinds people meet most often, based on titanium, cerium and silica, produced widely varying clearance [9]. Titanium and silicon are already in body tissue and in animal feed, so when only a fraction of a dose reaches an organ, telling it apart from that background becomes the hardest part of the experiment [14].
Callaghan, from ANSTO and the only member of the expert group from the Southern Hemisphere [6], described the problem this way: "Finding the nanoparticles within the body is like tipping a handful of sand onto a beach and then trying to pick out your own grains." [17] The fix, he said, is to mark the dose before it goes in: "The titanium we administered looks the same as the titanium that was already there. If you radiolabel the particles first, the nanoparticles of interest are the only grains that light up." [18]
That marking is what radioactivation does. The particle itself is irradiated so some of its atoms become radioactive, with nothing bonded to its surface to change how it behaves or to work loose [15]. The guidance rates the method only for studies of up to 90 days [16], while a single liver half-life in the injection studies ran to nearly three times that [11][2]. Following a poorly soluble particle all the way out of the body can outlast the best method for finding it.
What to watch
- Whether EFSA and ANSES commission new titanium dioxide safety studies built to the guidance's study design.
- Whether the OECD folds the nanoparticle sampling and duration rules into a revised binding test guideline.
- Whether laboratories develop tracers that hold up past 90 days to cover the longer clearance times.