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Source document:
SCCS (2012)

Summary & Details:
Media Consulta

Zinc oxide (nano form)

4. How have ZnO nanoparticles been tested for safety?

Zinc oxide nanoparticles to be used in sunscreens have been tested to see if they can cause any harm according to the standard testing procedure laid down in the SCCS "Notes of Guidance for the testing of cosmetic substances and their safety evaluation” (SCCS/1501/12). The experiments involved different types of ZnO nanoparticles (with or without different coatings of another chemical). The majority are toxicological tests on animals. Some, such as skin tests, resemble actual uses of sunscreen products to some extent. Others are simply standardised toxicological tests simply intended to see if a substance can cause any harm at all, usually if it is taken in large quantities. However, most of the tests have been developed to evaluate conventional chemicals and are not validated specifically for nanomaterials.

Acute toxicity tests showed few or no ill-effects in rats, even when force-fed 2000mg ZnO particles per kilogram of body weight. Some tests on mice did induce ill-effects at even larger doses.

Other tests reported include studies of skin irritation (in guinea pigs), of effects on mucous membranes around the eye (rabbits), and of skin sensitisation as an indication of potential to induce allergies. Apart from short-lived mild irritation in the eye test, the results were negative. For example, a test on 50 human volunteers, used suspensions of either coated or uncoated nanoparticles in corn oil. Those who took part were exposed the to a skin patched dosed with ZnO for three 24 hour days a week for three weeks. None of the volunteers showed any skin sensitisation over this time or when exposed to the same substances two weeks later.

Zinc oxide nanoparticles have also been tested for longer-term toxicity in animals, using both skin tests and experiments in which suspended particles are inhaled. There is a single study of repeated skin exposure in rats (ten per cent of body area treated for five days a week, over four weeks). This study showed no ill effects, but there was evidence of changes in collagen – an important connective protein found in skin and elsewhere. Collagen content in the rats’ skin and tail was reduced. It is possible this was due to skin penetration of nanoparticles after they had partially dissolved, and further chemical changes then producing reactive oxygen species which can damage proteins.

Injecting large doses (grams per kilo of body weight) of ZnO nanoparticles into the blood produces signs of liver damage in experimental rats.

Standard tests for damage to DNA – or for the potential to cause mutations – have also been applied to ZnO nanoparticles. No mutagenic effects have been reported, although it is uncertain how the bacteria used in most such tests interact with nanoparticles. Tests using human cells have recorded some DNA damage, which may be due to oxidative stress induced by local increase in concentrations of zinc when cells were exposed to high doses of nanoparticles in their culture medium.

Some substances have their mutagenic effects enhanced by radiation, including sunlight, which may be relevant to sunscreens in use. This has been tested in bacterial assays, with negative results, but again there may be doubts whether the nanoparticles have any contact with DNA in the bacteria used for the test.

At the moment, there is no conclusive evidence whether or not either micro or nano-sized zinc oxide particles can cause DNA damage or damage to the structure of chromosomes in cells. However, the evidence that little or no ZnO can pass through the skin in either form suggests that there is negligible risk of this kind of harm happening to any user of sunscreen.

Other tests reported include a different kind of exposure from skin application, swallowing or injection: inhalation. One study on human volunteers showed no acute toxic effects from a single exposure to ZnO nanoparticles in the air they were breathing. However, a study using rats did show that their lungs became inflamed when they inhaled ZnO nanoparticles for a longer period (five days). Some effects were still measurable in their lungs 25 days after exposure. This suggests that there may be a risk associated with any product in which ZnO nanoparticles are included in a spray.

For the safety evaluation of cosmetic substances the SCCS, after identification of the hazard, calculates a margin of safety, in order to consider whether the substance might pose a risk for human health. A No Observed Adverse Effect Level (NOAEL) is compared with plausible routes of actual exposure to work out the safety margin in use.

For ZnO the NOAEL derives from a study with human volunteers taking in zinc oxide by mouth, and is given as 0.166 mg per kilogram of body weight.

Taking into account an average amount of sunscreen applied, and the minimal amount which has been seen absorbed through the skin, calculation suggests that the margin of safety in use is 7.4. The margin for lipstick products which contain ZnO nanoparticles as sun protection is around half this, but still well above the required minimum of 1.0 for this particular case.

One major obstacle regarding the safety assessment of nanomaterials in cosmetic products is that there are currently limitations in the validity of some of the non-animal laboratory tests as they were developed for conventional (soluble) chemicals and not for nanoparticles.

The Three-Level Structure used to communicate this Scientific Committee on Consumer Safety (SCCS) opinion is copyrighted by Cogeneris SPRL.