In Vitro Risk Assessment for a Nano Fuel Additive: Tanks or No Tanks?

John Balbus, M.D., M.P.H., is Chief Health Scientist

The history of health and environmental impacts of fuel additives is not a pretty one. From tetra-ethyl lead to methyl tert-butyl ether (MTBE), we’ve learned the hard way that what goes in the tank ends up in our bodies and the environment sooner or later. Getting a thorough understanding of the potential risks of a new fuel additive at an early stage is essential to avoid a lot of harm, suffering, and economic costs down the line.

A new study by Park et al. has assessed the potential respiratory risks of a fuel additive called Envirox (nanoparticulate cerium oxide), giving it a clean bill of health based only on in vitro tests. Is this the vision of the future of risk assessment? Should we feel safe?

Nanoparticulate cerium oxide is touted as a solution to both global warming and particulate air pollution. Added to diesel fuel as a combustion catalyst, it has been shown to reduce both fuel consumption and fine particle concentration in diesel exhaust. But what happens when these tiny particles of cerium oxide blow out of the tail pipe?

The study by Park et al. uses short-term in vitro assays and exposure data to conclude negligible risk of oxidative stress and pulmonary inflammation from chronic exposure to Envirox-augmented diesel exhaust. The authors note that they have only examined oxidative stress and pulmonary inflammation and do not generalize more broadly about other potential health risks.

But does this really show Envirox is safe? The authors note, “this assessment assumes that the in vitro exposure data can be accurately projected to the in vivo situation.” What they don’t say is that it also assumes that short-term in vitro tests accurately predict effects from chronic exposure. Neither of these assumptions is seriously examined in the paper’s discussion, and I’ve questioned whether current in vitro tests can be relied upon to predict actual toxicity in a previous blog. But let’s assume for the moment that these assumptions are true.

Part of the concern with nanoparticles is the potential for translocation around the body, including to places where larger particles cannot go. Could cerium oxide nanoparticles reach and build up in the bone, kidneys, or spleen (areas where non-nano cerium oxide particles accumulate)? What about the developing brain (which other nanoparticles have been shown to access)? Can they harm those organs over time? Unfortunately, exposing lung slices in a petri dish can’t tell us about translocation or harm to these other organs.

In the 1920s, tetra-ethyl lead got the green light as a gasoline additive after a short-term test of effects in adults showed no harm. Of course, the worst effects of its use were chronic effects in children. More than twenty years after lead was taken out of gasoline, children are still affected by residual lead contamination in urban soils. We should be much smarter now.

Even if the present study can be extrapolated to suggest it is unlikely that Envirox will cause pulmonary oxidative stress and related harm in real people, we need to know much more than that before concluding that its widespread use as a fuel additive is safe.