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Nanotox

press-release

 

The Institute of Science in Society

Science Society Sustainability

http://www.i-sis.org.uk

 

General Enquiries sam

Website/Mailing List press-release

ISIS Director m.w.ho

===================================================

 

 

ISIS Press Release 04/12/03

Nanotox

*******

As nanotechnology is moving into producing tonnes of nanoparticles, Dr. Vyvyan

Howard (c.v.howard) explains why harmless materials become

dangerous when shrunk to the nanoscale.

 

A more technical fully referenced (http://www.i-sis.org.uk/full/NanotoxFull.php)

version of this article is posted on ISIS members’ website. Details here

(http://www.i-sis.org.uk/membership.php).

Introduction

 

The nano-technology industry has begun the bulk production of nanoparticles,

especially ultrafine particles for a range of commercial applications, from

titanium dioxide in sunscreens to carbon nanotubes for molecular electronics

(see " Nanotubes highly toxic " ( http://www.i-sis.org.uk/nanotubestoxic.php ) and

" Nanoshells cure or curse? " ( http://www.i-sis.org.uk/nanoshells.php ) this

series). Manufacturers are moving into production levels in excess of 100 tonnes

per annum.

Particles that can be breathed in are classified as: coarse (average diameter

less than 10micron); fine (average diameter less than 2.5 micron); and ultrafine

(average diameter less than one micron). One micron (m) is one millionth of a

metre and 1 000 nanometres (nm).

We have two defence mechanisms in the lung to deal with particles breathed in.

The first is a carpet of mucus that lines all but the most peripheral parts of

the lung. This carpet moves slowly upwards, carrying particles that have landed

on it, and is then swallowed. Particles that make it through this carpet of

mucus, which tend to be fine and ultrafine, get into the air sacs where gas

exchange between the air and the blood takes place. The surfaces of the air sacs

are patrolled by macrophages, scavenger cells that mop up particles. However,

macrophages appear to have difficulty recognising particles less than 70nm in

diameter, and in addition, they can be easily overwhelmed by too many particles.

It is illuminating to consider the types of particles we were exposed to

throughout the course of evolution. These consisted mainly of suspended sand and

soil particles and pollen grains; most of which are relatively coarse and are

trapped in the mucus before getting to the alveoli. There have always been

ultrafine particles (UFPs), mainly consisting of minute crystals of salt, which

become airborne through the action of the sea waves. These salt particles are

not toxic, however, because they are soluble in water. For particles less than

70 nm in diameter, there was nothing much in the air throughout our prehistory

of particular concern until we harnessed fire for use in our everyday life.

Research is revealing that when normally harmless bulk materials are made into

UFPs, they tend to become toxic. Generally, the smaller the particle, the more

reactive and toxic it becomes. This should come as no surprise, because that is

exactly how catalysts are prepared to enhance industrial chemical reactions. By

making particles of just a few hundred atoms, you create an enormous amount of

surface, which tends to become electrically charged and thus chemically

reactive. The upper size limit for the toxicity of UFPs is not fully known, but

is thought to lie between 65 and 200nm.

There is evidence that chronic exposure to particulate aerosols leads to

long-term health effects, primarily on the cardiovascular system. Most of these

studies have used coarse particles to assess the effects. More studies are now

using fine particles, though the question of whether it is more predictive of

harm than coarse particles is till being debated. There is also evidence that

short term effects from poor air quality is due to particle overloading. The

number of studies that have used UFPs is low, but there are indications that

UFPs are more hazardous than fine particles.

The main questions on the safety of nanoparticles are:

By what routes do UFPs get into the body and then where do they travel to?

What is the mechanism of toxic action and how does the reactive surface of UFPs

interact with the ‘wet biochemistry’ in the body?

What is the relative contribution of particle size versus particle composition

in the overall toxicity of UFPs?

Evidence of potential harm associated with UFPs comes from studies on toxicology

and absorption and fate of UFPs in whole animals and studies on mechanisms of

toxicity in cells and tissues.

 

Question 1. Routes of access into, and travel around, the body

***********************************************

First, it should be noted that there appears to be a natural ‘passageway’ for

nanoparticles to get into and subsequently around the body. This is through the

openings in the natural membranes, which separate body compartments. These

openings are between 40 and 100 nm in size and are thought to be involved in the

transport of macromolecules such as proteins, and on occasion, viruses. They

also happen to be about the right size for transporting UFPs. Most of the

research on that has been performed by the pharmaceutical industry interested in

finding ways of improving drug delivery to target organs. This is particularly

so for the brain, protected by the ‘blood brain barrier’. It appears that

chemists are able to design UFPs that can hoodwink certain membranes into

allowing ‘piggybacking’ of novel chemicals across membranes that would not be

possible otherwise, and UFPs have already been made that can enhance drug

delivery to the brain.

Although this can offer clear advantages, the obverse of this particular coin

needs to be considered. When environmental UFPs (as from traffic pollution) gain

unintentional entry to the body, it appears that there is a mechanism that can

deliver them to vital organs. The body is then ‘wide open’ to any toxic effects

that they can exert. The probable reason why we have not built up any defences

is that such environmental UFPs were not part of the prehistoric environment in

which we evolved and therefore there was no need to develop defensive mechanisms

against them.

There is considerable evidence that inhaled UFPs can gain access to the blood

stream and are then distributed to other organs in the body. This has been shown

for synthetically produced UFPs such as bucky-balls – a form of carbon in which

60 carbon atoms are arranged like a football - which accumulate in the liver.

Another possible portal of entry into the body is via the skin. A number of

sunscreen preparations now available have incorporated nanoparticle titanium

dioxide. Recent studies have shown that particles of up to 1 m in diameter

(within the category of UFPs) can get deep enough into the skin to be taken up

into the lymphatic system, while particles larger than that were excluded. The

implication is that UFPs can and will be assimilated into the body through the

skin. The exact proportion of those deposited on the skin, which will be

absorbed, remains unknown. Using post mortem human skin, it has been shown that

dextran beads 0.5 to 1m can penetrate the rough outer layer (stratum corneum) of

the skin when flexed. The penetration occurred in over 50 % of the samples if

flexing was continued for 1 hour. In a small proportion of cases, the beads got

as far as the dermis (inner layer of the skin).

 

Question 2. The mechanism of toxic action

********************************

Studies on laboratory animals have looked at the ability of UFPS to produce

inflammation in lungs after exposure to UFP aerosols. The degree to which UFPs

appear to be able to produce inflammation is related to the smallness of the

particles, the ‘age’ of the aerosol and the level of previous exposure. It has

been proposed that the chronic inhalation of particles can set up a low grade

inflammatory process that can damage the lining of the blood vessels, leading to

arterial disease.

Studies on cells have confirmed the increased ability of UFPs to produce free

radicals that cause cellular damage. This damage can be manifested in different

ways, including genotoxicity and altered rates of cell death.

 

Question 3. Particle size versus particle composition

****************************************

Early indications were that certain metals might be more toxic as UFPs than

other materials. Since then, other studies have shown very similar toxicities

between different materials when presented as UFPs, for example latex and

titanium dioxide. More recently, attention is being concentrated on the effects

of ultrafine carbon black. What seems clear from all the papers is that exposure

of living systems to UFPs tends to increase oxidative stress, and therefore, the

effect of small size is considerably more important for UFP toxicity than the

actual composition of the material.

 

Conclusions

*********

There is evidence that UFPs can gain entry to the body by a number of routes,

including inhalation, ingestion and across the skin. There is considerable

evidence that UFPs are toxic and therefore potentially hazardous. The basis of

this toxicity is not fully established but a prime candidate for consideration

is the increased reactivity associated with very small size. The toxicity of

UFPs does not appear to be very closely dependent on the type of material from

which the particles are made, although there is still much research to be done

before this question is fully answered.

Dr. Vyvyan Howard is histo-toxicologist at University of Liverpool. A version of

this article first appeared as annex to " No Small Matter II: The Case for a

Global Moratorium " www.etcgroup.og

 

 

===================================================

This article can be found on the I-SIS website at

http://www.i-sis.org.uk/Nanotox.php

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General Enquiries sam

Website/Mailing List press-release

ISIS Director m.w.ho

 

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