Fabrizio Zago ha scritto:Ciao Biopietro,
come sempre hai perfettamente centrato il mio pensiero e ne sono vagamente preoccupato, non è che la prossima volta mi leggi il codice segreto della mia carta di credito?
Nella nuova edizione metterò due ZnO con due classificazioni "motivate".
Ciao
Fabrizio
Dai Fabrizio, prima di assegnare i tuoi semaforini rossi all’ZnO nano nel nuovo biodizionario, leggi questo articolo quando hai tempo e dimmi cosa ne pensi. Mi sembra che gli autori di questa ricerca dimostrino con dati alla mano che sia il ZnO che TiO2 nano sono sicuri nell’uso come filtri solari .
Grazie
Nohynek GJ, Dudour EK, Roberts MS: Nanotechnology, cosmetics and the skin; is there a
health risk? Skin Pharmacol & Physiol 2008, 21: 136-149.
Summary and comment
This is a review article (107 references) addressing what are described as key questions
regarding topically applied nano-material that are, “(a) are they absorbed and (b), if so, are
they intrinsically toxic. Specific questions concerning the safety of nano-material (particles)
in cosmetic products and sunscreens include the following: (a) do cosmetic formulations
containing nano-sized features (vesicles or droplets) enhance the skin penetration of cosmetic
ingredients, thereby increasing the risk of human skin sensitization or systemic exposure? (b)
do nano-sized cosmetic formulations pose new risks when compared with those of traditional
cosmetic products? (c) do topically applied insoluble nanoparticles (NP) remain on the skin
surface or are they able to pass the skin barrier of normal or compromised skin to gain access
to the systemic compartments of the organism? (d) are insoluble nanoparticles in sunscreens
intrinsically more hazardous than larger particles, ie. microparticles or bulk material”.
In this review, sunscreens with NP TiO2 and ZnO were assessed at length, with a conclusion
reached indicating that in vivo toxicity tests showed that NP TiO2 and ZnO were essentially
non-toxic. Also, a significant number of in vivo and in vitro studies suggest that NP TiO2 and
ZnO do not penetrate into or through human skin. This article cited a reference (ref 35 of this
TGA review) which indicated NP TiO2 behaved in a similar manner to micro-TiO2 in a
series of studies considered to be a base set for toxicity testing (in vitro and in vivo
cytotoxicity, genotoxicity, photogenotoxicity, acute toxicity, sensitization and
ecotoxicology), and TiO2 presented as a low hazard.
Some in vitro studies reported issues with NP cell uptake, oxidative cell damage or
genotoxicity, which were suggested as possibly being secondary to phagocytosis of cells
exposed to excessive particle concentration.
The authors included sections on nanotechnology and NP in cosmetics and sunscreens, and
local and systemic exposure following dermal (structure described) application of nanomaterial.
A description of TiO2 and ZnO noted that they reflect and scatter UV light most
efficiently over a size range of 60-120nm, while ZnO is generally used over a particle size
range of 30-200nm. TiO2 particles for use in sunscreens has a size of 14 nm that forms stable
micrometer sized aggregates. Mention was made of nano-particle surface treatment (occurs
frequently) with agents such as aluminium oxide or silicon oils to improve dispersion in
sunscreens. A description of the structure of skin was presented along with a comparative
analysis of dermal penetration rates showing rabbit skin>rat>pig>monkey>man; it was noted
that pig and rat skin is up to 4 and 9-11 times more permeable than human skin, respectively.
This information on variability of skin penetration highlighted the need for caution when
interpreting results from animal studies in relation to effects in humans.
On the issue of potential passive penetration of NP-TiO2 or ZnO, the authors provided an
extensive review of studies including nano-material other than TiO2 or ZnO and came to the
conclusion that all available evidence supports the notion that the size range of NP agents in
sunscreens do not penetrate into the skin or produce systemic exposure. Studies on other
nano-materials examined fluorescent dextran beads, soil particles (0.4-0.5μm), quantum dots,
fluorescent nano-capsules and phenylalanine-based fullerene amino acid (3.5nm). The
authors noted that in the studies with extremely small fullerenes there was a “grey zone”
regarding passive skin penetration. The fullerenes mentioned are extremely small
nanoparticles compared with the NP used in sunscreens, which have consistently shown not
to penetrate into or through skin.
Possible skin penetration from nano-sized vesicle-type or other formulations (nanosomes,
liposomes, niosomes, nano-emulsions, nanocapsules and solid lipid NP was described. It was
noted that most of our knowledge of skin penetration of these materials comes from research
on transdermal drug delivery (TDD) systems. The authors reviewed studies on various nanosized
systems used in TDD and concluded, “these data suggest that vesicle materials, as well
as vesicle size, may affect the skin penetration of liposome- or niosome-encapsulated drugs to
some degree, although the penetration rate of the active ingredient is not enhanced by a
reduced vesicle size”. Cited studies indicated that the skin penetration of some drugs may be
enhanced, but only for particular and suitable drugs; enhancement of skin penetration appears
to be dependent on a number properties of the drug and not just size. The authors noted that
the knowledge gained from the TDD systems does not change the belief that passive skin
penetration of NP TiO2 or ZnO is extremely unlikely.
Local and systemic toxicity of NP used in sunscreens was examined in this review. One study
using murine fibroblasts and macrophages in an analysis of cytotoxicity of insoluble ceramic
particle (NP and micro) showed that the larger sized particles were more toxic than the
smaller particles. Results from this study led the authors to suggest that particle phagocytosis
by cells was a primary link to particle mediated cytotoxicity and not necessarily size of
particle; this belief appeared to be supported by further studies discussed in the review.
Further examples of physiological responses of cells to excessive levels of insoluble particles
were presented, which may culminate in oxidative cell damage and possibly genotoxicity
outcomes. The complex nature of in vitro testing was discussed, which highlighted the
variability associated with this approach.
A concluding statement noted that,
“in vitro studies
that claim discovery of intracellular penetration and oxidative stress-related toxicity of nanoor
microparticles in cultured mammalian cells should be interpreted with great caution in
terms of their relevance for intact organisms. This view is supported by consensus
recommendations of a recent workshop on toxicology testing of NM that concluded that
evaluation of the safety of nanomaterials should be primarily based on in vivo toxicity
models, rather than use of in vitro assays”.The issue of cytotoxicity, phototoxicity and photogenotoxicity of TiO2 and ZnO micro- and nanoparticles was discussed in this review. Specific information on the genotoxicity and
photogenotoxicity of TiO2 (anatase and rutile forms) was presented in tabular form, which
indicated TiO2 did not (negative) induce genotoxicity/photogenotoxicity in assays (11 assays
summarized) assessing forward/reverse mutations, chromosomal aberrations or neutral red
uptake as a measure of phototoxicity. TiO2 tested included micro-and nano-sized particles,
with no difference in safety profile for these materials. A second table summarizing the
genetic and photogenetic toxicity of micro-or nano-sized ZnO was presented, which showed
ZnO to clastogenic and photoclastogenic in vitro mammalian cell cultures (CHO and V-79
cells). However, the authors cited a reference (EU document) indicating that ZnO was not
clastogenic in vivo, and was shown to be non-photoreactive, non-phototoxic or nonphotosensitising.
An analysis of these findings led the authors to suggest the perceived
photogenotoxicity was probably due to UV-mediated, enhanced susceptibility of the
mammalian cells to ZnO.
In the area of general toxicity of insoluble NP after oral or topical administration the authors
noted that the safety of sunscreens and their ingredients is regulated in the EU and USA (and
relevant Health Authorities in other countries), with sunscreens containing micro- and nanosized
TiO2 and ZnO undergoing numerous pre-clinical evaluation for safety and efficacy.
Mention was made of a study (described previously) which indicated NP TiO2 behaved in a
similar manner to micro-TiO2 in a series of studies considered to be a base set for toxicity
testing (in vitro and in vivo cytotoxicity, genotoxicity, photogenotoxicity, acute toxicity,
sensitization and ecotoxicology), and TiO2 presented as a low hazard.
A final section of this review focused on NP and compromised skin and indicated that, “there
is little evidence suggesting slightly compromised skin has a greater susceptibility to skin
penetration of topically applied substances”. Interestingly, an example given cited a study
that showed no skin penetration (absorption) of NP TiO2 through normal and psoriatic
human skin. It could be expected that skin diseases that cause a rupture in the stratum
corneum diminishing the normal protective barrier could result in an increase skin
penetration. A final example given by the authors noted that injected (subcutaneous) NP
TiO2, by-passing the skin barrier, was found to be non-toxic suggesting that even if NP TiO2
did penetrate the skin it would not be a hazard by this route of administration.
Conclusion:
Currently, there is no in vivo evidence to indicate possible toxicity of nanoparticulate TiO2 or
ZnO in people using sunscreens. To date, the current weight of evidence indicates the
particles remain on the surface of the skin and in the outer dead layer (stratum corneum) of
the skin.OTC Medicines Section
Therapeutic Goods Administration
July 2009
I love ossido di zinco
Biopietro