Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.

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Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles

IN 1974, the International Radiation Protection Association (IRPA) formed a working group on non-ionizing radiation (NIR), which examined the problems arising in the field of protection against the various types of NIR. At the IRPA Congress in Paris in 1977, this working group became the International Non-Ionizing Radiation Committee (INIRC). In cooperation with the Environmental Health Division of the World Health Organization (WHO), the IRPA/INIRC developed a number of health criteria documents on NIR as part of WHO’s Environmental Health Criteria Programme, sponsored by the United Nations Environment Programme (UNEP). Each document includes an overview of the physical characteristics, measurement and instrumentation, sources, and applications of NIR, a thorough review of the literature on biological effects, and an evaluation of the health risks of exposure to NIR. These health criteria have provided the scientific database for the subsequent development of exposure limits and codes of practice relating to NIR. At the Eighth International Congress of the IRPA (Montreal, 18–22 May 1992), a new, independent scientific organization—the International Commission on Non-Ionizing Radiation Protection (ICNIRP)—was established as a successor to the IRPA/INIRC. The functions of the Commission are to investigate the hazards that may be associated with the different forms of NIR, develop international guidelines on NIR exposure limits, and deal with all aspects of NIR protection. Biological effects reported as resulting from exposure to static and extremely-low-frequency (ELF) electric and magnetic fields have been reviewed by UNEP/ WHO/IRPA (1984, 1987). Those publications and a number of others, including UNEP/WHO/IRPA (1993) and Allen et al. (1991), provided the scientific rationale for these guidelines. A glossary of terms appears in the Appendix.

Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields (up to 300 GHz)

IN THIS document, guidelines are established for the protection of humans exposed to electric and magnetic fields in the low-frequency range of the electromagnetic spectrum. The general principles for the development of ICNIRP guidelines are published elsewhere (ICNIRP 2002). For the purpose of this document, the low-frequency range extends from 1 Hz to 100 kHz. Above 100 kHz, effects such as heating need to be considered, which are covered by other ICNIRP guidelines. However, in the frequency range from 100 kHz up to approximately 10 MHz protection from both, low frequency effects on the nervous system as well as high frequency effects need to be considered depending on exposure conditions. Therefore, some guidance in this document is extended to 10 MHz to cover the nervous system effects in this frequency range. Guidelines for static magnetic fields have been issued in a separate document (ICNIRP 2009). Guidelines applicable to movement-induced electric fields or time-varying magnetic fields up to 1 Hz will be published separately. This publication replaces the low-frequency part of the 1998 guidelines (ICNIRP 1998). ICNIRP is currently revising the guidelines for the high-frequency portion of the spectrum (above 100 kHz).

ICNIRP Guidelines for limiting exposure to time-varying electric and magnetic fields (1 Hz to 100 kHz).

Imaging iron stores in the brain using magnetic resonance imaging.

Magnetotactic Bacteria and Magnetosomes

Although the mineral magnetite (Fe3O4) is precipitated biochemically by bacteria, protists, and a variety of animals, it has not been documented previously in human tissue. Using an ultrasensitive superconducting magnetometer in a clean-lab environment, we have detected the presence of ferromagnetic material in a variety of tissues from the human brain. Magnetic particle extracts from solubilized brain tissues examined with high-resolution transmission electron microscopy, electron diffraction, and elemental analyses identify minerals in the magnetite-maghemite family, with many of the crystal morphologies and structures resembling strongly those precipitated by magnetotactic bacteria and fish. These magnetic and high-resolution transmission electron microscopy measurements imply the presence of a minimum of 5 million single-domain crystals per gram for most tissues in the brain and greater than 100 million crystals per gram for pia and dura. Magnetic property data indicate the crystals are in clumps of between 50 and 100 particles. Biogenic magnetite in the human brain may account for high-field saturation effects observed in the T1 and T2 values of magnetic resonance imaging and, perhaps, for a variety of biological effects of low-frequency magnetic fields.

https://www.pnas.org/content/pnas/89/16/7683.full.pdf

Magnetite biomineralization in the human brain.

Due to the apparent lack of a biophysical mechanism, the question of whether weak, low-frequency magnetic fields are able to influence living organisms has long been one of the most controversial subjects in any field of science. However, two developments during the past decade have changed this perception dramatically, the first being the discovery that many organisms, including humans, biochemically precipitate the ferrimagnetic mineral magnetite (Fe_(3)S_4). In the magnetotactic bacteria, the geomagnetic response is based on either biogenic magnetite or greigite (Fe_(3)S_4), and reasonably good evidence exists that this is also the case in higher animals such as the honey bee. Second, the development of simple behavioral conditioning experiments for training honey bees to discriminate magnetic fields demonstrates conclusively that at least one terrestrial animal is capable of detecting earth-strength magnetic fields through a sensory process. In turn, the existence of this ability implies the presence of specialized receptors which interact at the cellular level with weak magnetic fields in a fashion exceeding thermal noise. A simple calculation shows that magnetosomes moving in response to earth-strength ELF fields are capable of opening trans-membrane ion channels, in a fashion similar to those predicted by ionic resonance models. Hence, the presence of trace levels of biogenic magnetite in virtually all human tissues examined suggests that similar biophysical processes may explain a variety of weak field ELF bioeffects.

/pdf/magnetite-in-human-tissues-a-mechanism-for-the-biological-3hyw12d80y.pdf

Magnetite in human tissues: a mechanism for the biological effects of weak ELF magnetic fields.

http://link.springer.com/content/pdf/10.1007/978-3-642-71526-6_35.pdf

Atsuko Kobayashi-Kirschvink

Papers

Magnetite biomineralization in the human brain.

Magnetite in human tissues: a mechanism for the biological effects of weak ELF magnetic fields.

A Mathematical Model for Magnetic Navigation by Animals