Parabens in Perspective: Part IX

Having reported on the SCCS Final Opinion on parabens, I had decided that I would call it a day on writing articles on this subject. However, Part 7 provoked an unusually lively discussion, with some interesting points being highlighted, and I am addressing these points by extending the series with another 3 articles.

This article will address a study on oxidative damage to skin by parabens, leading to a claim of accelerated aging. The article below seems to be the only study addressing this point, and I quote the entire abstract of the study here:

Combined Activation of Methyl Paraben by Light Irradiation and Esterase Metabolism toward Oxidative DNA Damage.

Chem Res Toxicol. 2008 Jul 26;

Authors: Okamoto Y, Hayashi T, Matsunami S, Ueda K, Kojima N

Methyl paraben (MP) is often used as a preservative in foods, drugs, and cosmetics because of its high reliability in safety based on the rapid excretion and nonaccumulation following administration. Light irradiation sometimes produces unexpected activity from chemicals such as MP; furthermore, there is ample opportunity for MP to be exposed to sunlight. Here, we investigated whether MP shows DNA damage after sunlight irradiation. Two major photoproducts, p-hydroxybenzoic acid (PHBA) and 3-hydroxy methyl paraben (MP-3OH), were detected after sunlight irradiation to an aqueous MP solution. Both photoproducts were inactive in the in vitro DNA damage assay that measures oxidized guanine formed in calf thymus DNA in the presence of divalent copper ion, a known mediator of oxidative DNA damage. Simulated MP metabolism using dermal tissues after light irradiation produced these two photoproducts, which reacted with a microsomal fraction (S9) of the skin. A metabolite from MP-3OH, not PHBA, caused distinct DNA damage in the in vitro assay. This active metabolite was identified as protocatechuic acid, a hydrolyzed MP-3OH product. In addition, NADH, a cellular reductant, enhanced DNA damage by approximately five times. These results suggest that reactive oxygen species generated by the redox cycle via metal ion and catechol autoxidation are participating in oxidative DNA damage. This study reveals that MP might cause skin damage involving carcinogenesis through the combined activation of sunlight irradiation and skin esterases.

My observations:

The production of photoproducts in an aqueous solution will be much more marked than in a skin cream, for two major reasons:

1)      The exposure of methylparaben to the light source will be considerably greater in aqueous solution than it will ever be in a skin cream as the light source penetrates through the entire liquid in the aqueous solution and, additionally, the liquid is much more mobile with a greater probability of contact between the relevant molecules involved in the process.

2)      Much of the methylparaben in the skin cream may be absorbed into the skin and broken down by skin esterases before any significant photodegradation could take place. According to Jewell et al (Tox. & Appl. Pharmacol. 225; 221 – 228), only 5% methylparaben remains intact on the skin after 6 hours of the application.

The major metabolite of methylparaben from skin exposure is 4-hydroxybenzoic acid, and this is already absorbed within the skin, is not exposed to light irradiation and, additionally, is determined in this study to be inactive in the in vitro DNA damage assay.

The exposure of methylparaben to light is exaggerated in this synopsis, as skin products are generally thinly dispersed on the skin, and any components that are absorbed are likely to be asbsorbed fairly rapidly.

The “guilty” species in this study – protocatechuic acid – is a metabolite of 3-hydroxymethylparaben, ie this is two stages removed from the normal metabolic breakdown process observed when methylparaben is applied to the skin.

It seems highly unlikely that protocatechuic acid would be generated from the use of methylparaben in skin products, and to state that methylparaben might cause skin damage by this mechanism is highly speculative. It is worth noting that the authors use the term “might” [cause skin damage], rather than claiming this as a fact. This is, in effect, a highly speculative study. Sadly, this has not stopped many observers claiming that parabens cause skin aging as a proven fact.

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