Opinion on Zinc oxide (nano form), COLIPA S 76

The EU Scientific Committee on Consumer Safety assessed nano zinc oxide as a UV filter at up to 25 percent. It concluded that nano zinc oxide with the characteristics in the dossier does not pose a risk after dermal application, and that sprayable products leading to inhalation cannot be considered safe. On impurities it states: “No information has been provided on the presence of impurities/contaminants”. From reported purity of 99 percent or more it infers impurities of 1 percent or less, with no metal-specific data. On dermal absorption it concludes that zinc oxide nanoparticles do not penetrate skin. It accepts that a very small proportion of zinc ions may become systemically available. It reports “no significant differences … between damaged skin versus normal healthy skin” in the studies it reviewed.

Key numbers

Purity is reported as ≥99.0 percent for the various nanomaterials and ≥96 percent for one submitted material (section 3.1.4). One test material of ≥96 percent lacked purity data. Water solubility of four uncoated nano zinc oxides was 20 to 47 mg/L as zinc. Pigmentary zinc oxide was <0.1 mg/L in water and 35 mg/L in cell-culture medium. The committee estimates maximum solubility at around 50 mg/L.

Conditions of the assessment (PDF p. 26): purity ≥ 99 %, wurtzite, D50 between 30 and 55 nm with D1 above 20 nm, uncoated or listed silane or dimethicone coatings, solubility below 50 mg/L. These were revised by the 2014 addendum.

In vitro human skin with 1 percent zinc oxide emulsions showed no penetration at a zinc limit of detection of 0.01 ppm. In another in vitro study, zinc in receptor fluid over 24 hours was 0.09 ± 0.04 µg/cm2 (untreated) and 0.22 ± 0.12 µg/cm2 (placebo), and treated membranes gave less than 0.03 percent of the applied dose. The committee adopted 0.03 percent as the absorbed fraction. In pig skin in vitro, receptor-fluid zinc was 0.8, 0.8 and 1.4 percent and absorbed dose 1.5, 1.6 and 2.3 percent of the applied dose, but untreated and vehicle-treated skin gave comparable values. In the human beach trial with zinc-68 labelled sunscreen, blood tracer rose 0.1 to 0.8 percent (mean increase about 0.4 percent in the nanoparticle group), and total tracer in blood was less than 0.001 percent of the applied dose. The tracer in blood was 8.6 to 30.8 µg in the highest male group against about 12 mg of zinc in whole blood (PDF p. 55).

The committee quotes the 2004 EU Risk Assessment Report: a default dermal absorption of 2 percent for zinc solutions or suspensions, an oral NOAEL of 50 mg Zn2+/day in women, and an internal NOAEL of 10 mg Zn2+/day. Its own margin of safety for sunscreen at 25 percent nano zinc oxide is 7.4, from 1.35 mg absorbed per day and a systemic exposure dose of 0.0225 mg/kg bw/d in a 60 kg adult. The oral zinc oxide NOAEL is printed as “50 mg /bw day” (PDF p. 96), missing the kilogram.

Methods (brief)

The opinion is a structured review of the applicant dossier and published literature: physico-chemical data, toxicology and dermal penetration. The absorption figures come from in vitro Franz-cell studies on human and pig skin and from stable-isotope trials in volunteers. Secretariat contact: Sanco-SCCS-Secretariat@ec.europa.eu.

Evidence fitness

The opinion supports two statements. The EU safety assessment of nano zinc oxide contains no heavy-metal impurity data. Zinc from zinc oxide crosses adult skin in very small amounts. The damaged-skin models it reviewed were tape-stripped or UVB-exposed skin. In one pig study, UVB-damaged skin “did not enhance the penetration of Zn” (PDF p.49). The opinion does not address diaper creams, prolonged occlusion, infant skin or eroded dermatitis. A mouse study in this collection reports the opposite effect of UVB (UVB exposure enhanced the dermal penetration of zinc oxide nanoparticles and induced inflammatory responses through oxidative stress mediated by MAPKs and NF-κB signaling in SKH-1 hairless mouse skin). The margin-of-safety table multiplies by the zinc oxide mass, not the zinc ion mass, which makes the printed figure conservative compared with a zinc-ion calculation. The dermal figures are for adult intact skin and for zinc itself, not for metal impurities carried by the particles.

Limitations

The study header for the beach trial gives 20 volunteers split 11 and 9, while the narrative says two groups of ten. One solubility statement prints particle sizes in millimetres, which is implausible for these materials. The primary papers behind the absorption figures were not in this collection. No infant, diaper-area or barrier-impaired skin data. Conditions superseded in part by the 2014 addendum and Annex VI entry 30a.

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