Particles on the Brain

BrooklynDodger continues with the big story of the 21st century in occupational and environmental health. That story is the lung toxicity of particles without specific toxicity [in contrast to silica and asbestos] and the additional ability of ultrafine particles to penetrate the lungs into the rest of the body.

The burst of work on lung toxicity of "non-toxic" particles began following the observation that inhaled diesel particulate matter was carcinogenic in the rat, about 100 times as potent as cigarette smoke. But, clean carbon particles [carbon black] had potency equivalent to DPM.

The burst of work on penetration of ultra fine particles was prompted by the observation in people of increased cardiac mortality with increased particulate exposure in community studies.

In this study, the investigators found two things at carbon particle exposures very low compared to occupational limits. OSHA permits respirable particle exposures of 5000 micrograms per cubic meter, 8 hours a day for a working lifetime. Exposures in this study were 160 micrograms per cubic meter for 6 hours. EPA permits small particle exposures of 15 micrograms per cubic meter, but increased mortality is observed at these levels.

First, particles persisted in the lungs for a week, and certainly much longer. Second, these particles penetrated the brain, in spite of the blood brain barrier.

The following paraphrases the abstract, followed by the full reference:

We generated ultrafine elemental radioactive carbon particles at a concentration of 160 microg/m(3). Rats were exposed for 6 h. Lung concentration decreased from 1.39 microg/g (day 1) to 0.59 microg/g by 7 days postexposure. [Dodger: initially deposited carbon particles were only ½ cleared out of the lungs in 1 week.] Day 1 (13)C concentrations of cerebrum and cerebellum were also significantly increased but the increase was inconsistent, significant only on one additional day of the postexposure period…. We conclude from our study that the CNS can be targeted by airborne solid ultrafine particles and that the most likely mechanism is from deposits on the olfactory mucosa of the nasopharyngeal region of the respiratory tract and subsequent translocation via the olfactory nerve.


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Inhal Toxicol. 2004 Jun;16(6-7):437-45.

Translocation of inhaled ultrafine particles to the brain.Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C.Department of Environmental Medicine, University of Rochester, Rochester, New York 14642, USA.
gunter_oberdorster@urmc.rochester.edu

Ultrafine particles (UFP, particles <100>

Our previous rat studies have shown that UFP can translocate to interstitial sites in the respiratory tract as well as to extrapulmonary organs such as liver within 4 to 24 h postexposure. There were also indications that the olfactory bulb of the brain was targeted. Our objective in this follow-up study, therefore, was to determine whether translocation of inhaled ultrafine solid particles to regions of the brain takes place, hypothesizing that UFP depositing on the olfactory mucosa of the nasal region will translocate along the olfactory nerve into the olfactory bulb. This should result in significant increases in that region on the days following the exposure as opposed to other areas of the central nervous system (CNS). We generated ultrafine elemental (13)C particles (CMD = 36 nm; GSD = 1.66) from [(13)C] graphite rods by electric spark discharge in an argon atmosphere at a concentration of 160 microg/m(3). Rats were exposed for 6 h, and lungs, cerebrum, cerebellum and olfactory bulbs were removed 1, 3, 5, and 7 days after exposure. (13)C concentrations were determined by isotope ratio mass spectroscopy and compared to background (13)C levels of sham-exposed controls (day 0). The background corrected pulmonary (13)C added as ultrafine (13)C particles on day 1 postexposure was 1.34 microg/lung. Lung (13)C concentration decreased from 1.39 microg/g (day 1) to 0.59 microg/g by 7 days postexposure. There was a significant and persistent increase in added (13)C in the olfactory bulb of 0.35 microg/g on day 1, which increased to 0.43 microg/g by day 7. Day 1 (13)C concentrations of cerebrum and cerebellum were also significantly increased but the increase was inconsistent, significant only on one additional day of the postexposure period, possibly reflecting translocation across the blood-brain barrier in certain brain regions. The increases in olfactory bulbs are consistent with earlier studies in nonhuman primates and rodents that demonstrated that intranasally instilled solid UFP translocate along axons of the olfactory nerve into the CNS. We conclude from our study that the CNS can be targeted by airborne solid ultrafine particles and that the most likely mechanism is from deposits on the olfactory mucosa of the nasopharyngeal region of the respiratory tract and subsequent translocation via the olfactory nerve. Depending on particle size, >50% of inhaled UFP can be depositing in the nasopharyngeal region during nasal breathing. Preliminary estimates from the present results show that approximately 20% of the UFP deposited on the olfactory mucosa of the rat can be translocated to the olfactory bulb. Such neuronal translocation constitutes an additional not generally recognized clearance pathway for inhaled solid UFP, whose significance for humans, however, still needs to be established. It could provide a portal of entry into the CNS for solid UFP, circumventing the tight blood-brain barrier. Whether this translocation of inhaled UFP can cause CNS effects needs to be determined in future studies.