ISIS Report 18/11/03
Nanotubes Highly Toxic
An entire molecular electronics industry is poised to take off, much
of it on the back of carbon nanotubes. But new research is raising alarm.
Nanotubes are highly damaging to the lungs of mice.
Dr. Mae-Wan Ho calls for a moratorium
until proper safeguards can be put in place.
Molecular electronics is making headlines. Much of it is based on
single-wall carbon nanotubes, which have many other potential applications as
strong, lightweight material in the aerospace and defence industries. Nanotubes
are now manufactured in bulk. Dr. Smalley (Nobel laureate and a pioneer in
carbon nanotube research) predicted that hundreds of thousands of tons of the
stuff could be produced in 5 to 10 years and "in time, millions of tonnes of
nanotubes will be produced worldwide every year". But enthusiasm for research
and development has run way ahead of safety precaution.
Unprocessed nanotubes are very light, and could become airborne and
potentially reach the lungs. Researchers in the Space and Life Sciences of NASA
Johnson Space Center, Wyle Laboratories, and the Department of Pathology and
Laboratory Medicine, University of Texas Medical School, in Houston, Texas,
USA, investigated the toxicity of carbon nanotubes to the lungs, by introducing
them into the trachea of mice under anaesthesia.
The results are alarming. Five of the mice treated with high dose of one
kind of nanotubes died within 7 days. All nanotube products induced epitheliod
granulomas tumour-like nodules of bloated white blood cells in the
lining of the lungs - and in some cases inflammation of the lungs at 7 days.
These persisted and became more pronounced in animals that were sacrificed at
90days. The lungs of some animals also showed inflammation around the bronchi,
and extensive necrosis (tissue death).
Carbon nanotubes, the researchers conclude, are "much more toxic than
carbon black and can be more toxic than quartz, which is considered a serious
occupational health hazard in chronic inhalation exposures."
The researchers had used nanotubes produced under different conditions
containing different heavy metals. Samples of raw and
purified nanotubes both contained iron, while a third nanotube
product contained nickel and yttrium.
A suspension containing 0, 0.1 or 0.5 mg of carbon nanotubes was
introduced into the trachea of the mice. As added controls, groups of mice were
given a suspension of carbon black or of quartz. The mice were killed at 7days
or 90days after the single treatment, in order to examine the lungs.
Nanotubes are neither water-soluble nor wettable, and all the products
were extremely difficult to disperse; and ultrasound as well as
heat-inactivated mouse serum had to be used.
Graphite the most similar form of carbon to nanotubes - does not
possess the electrical properties and fibrous structure of the nanotubes, and
its permissible inhalation exposure limit set by the occupational safety and
health administration (OSHA) is 15mg/m3 of total dust and
5mg/m3 for the respirable (capable of being inhaled)
fractions. It is well known that the geometry and surface chemistry of
particulates can play an important role in causing lung toxicity.
All animals treated with 0.1mg per mouse of nickel-yttrium containing
nanotubes showed no overt clinical signs. But 5 of 9 mice treated with 0.5mg
died: 2/4 within the 7day group and 3/5 in the 90day group. All deaths occurred
4 to 7 days after receiving the nanotubes. Deaths generally preceded by
lethargy, inactivity and body-weight losses. These symptoms were also seen in
the high dose mice that survived. Mice in the 90day group lost 27% of their
body weight by the first week. Symptoms in the two surviving mice disappeared
after one week and the animals started to gain weight.
The iron-containing nanotubes (both raw and purified) did not cause
deaths in the mice. Mild signs of inactivity, hypothermia, and occasionally
shivering were most noticeable 8 to 12h after treatment with the raw nanotubes,
and symptoms disappeared soon after this time. There were no body weight losses
with the raw or purified iron-containing nanotubes.
Under the microscope, the lungs of dead animals in the high dose group
showed large aggregates of particles in macrophages (large white blood cells
that eat foreign particles) in the alveolar space (air sac), some
of the aggregates were also found in spaces between cells, forming granulomas
(tumour-like nodules consisting of the bloated white blood cells). There were
also signs of inflammation. Granulomas were not detected in mice given the low
dose of the nickel-yttrium nanotubes. The lungs of mice given high dose of
either raw or purified iron-containing nanotubes showed prominent granulomas at
7days. Most of these nodules were located beneath the bronchial epithelium
(lining) and were present throughout the lung fields. Some appeared to extend
into the bronchi as polyps (irregular growths) .
The granulomas consisted of macrophages laden with black particles, and
had very few other white blood cells. Some of the lungs from mice given high
doses of the nanotubes appeared grossly abnormal at 90 days. The lung lesions
were generally more pronounced than those given the high dose at 7 days; some
also had necrosis (tissue death), and extensive inflammation. Granulomas and
other pulmonary lesions were also seen in some of the mice given the lose doses
of nanotubes, but to a milder degree.
Heat inactivated serum did not produce any clinical signs, nor gross or
microscopic lesions. The mice of the carbon black or quartz treated controls
also did not show any clinical signs that could be attributed to treatment.
Quartz at high dose (0.5 mg) induced an increase in the number of macrophages
in the lungs, and some of these cells contained particles. Quartz also produced
mild to moderate inflammation. The results for the 7day and 90day groups were
generally similar. One mouse in the 7day group had a low-grade granuloma
reaction; and the mice in the high dose 90day group had increased clusters of
lymphocytes surrounding the bronchi (sign of inflammation).
Purified nanotubes contained only a small amount of metal (2% by
weight). Insoluble iron and iron compounds are low in toxicity, so the results
strongly indicate that the nanotubes themselves induced the granulomas. Another
research group had found similar results previously in rats.
The deaths of 5 mice may have been caused by nickel and yttrium in the
nanotube sample, as they did not occur in the other samples of nanotubes.
One of the major effect of nanotubes is that they moved rapidly through
the walls of the air sacs, in contrast to carbon black. Nanotubes are totally
insoluble and non-biodegradable fibres, and it is well known that the
pathogenicity of a fibre in the lungs directly correlates with its persistence.
Graphite toxicity is known as graphite pneumoconiosis, characterized by
granulomas, emphysema, tissue death and hardening of the blood vessels, among
other symptoms, and has been long recognized in a large number of workers
involved in mining and processing graphite. But theses nanotube samples did not
These results show that a single exposure is enough to trigger serious
effects including deaths. No safety tests have yet been carried out, especially
in the longer-term, on a range of other nanoparticles used, some of them in
intended medical procedures. Civil society watchdogs such as the ETC Group have
called for a moratorium on nanotechnology research and development.
The present findings certainly justify a moratorium on research
involving nanotubes, if not all nanoparticles, until proper safeguards can be
put in place, and safety tests carried out in the meantime.
Lam CW, James JLt, McCluskey R and Hunter RL. ToxSci Advance Access
published 26, 2003. Pulmonary toxicity of single-wall carbon nanotubes in mice
7 and 90 days after intratracheal instillation.