Why don’t we use isoamyl-p-methoxycinnamate (amiloxate)?

Amiloxate is an ester formed by the reaction between methoxycinnamic acid and 2-ethylhexanol, with the molecular formula C18H26O3. Its structure comprises a branched alkyl chain and an aromatic core substituted by a methoxy group (-OCH₃), imparting the molecule selective UV absorption properties. Isoamyl p-methoxycinnamate combines with other filters, such as titanium dioxide or oxybenzone, to broaden its protection spectrum. In Europe, the maximum permitted concentration of amiloxate in sun care products is set at 10%, in accordance with Annex VI of Regulation (EC) No 1223/2009 on cosmetic products. In other regions of the world, such as the United States or Asia, regulations vary.

In the European Union, Australia, China, India and South Africa, amiloxate may be used at a maximum concentration of 10%, whereas this filter is not permitted in the United States, Canada and Japan.

Amiloxate is recognised for its ability to protect hair and skin from the sun’s harmful rays. However, it is criticised for the following reasons:

What is the impact of isoamyl p-methoxycinnamate on health?

Several in vitro studies have revealed the potential cytotoxicity of isoamyl-p-methoxycinnamate. In human liver cell models (SMMC-7721), exposure to amiloxate leads to a significant decrease in cell survival and inhibition of proliferation. This decline is accompanied by a marked increase in reactive oxygen species, a loss of mitochondrial membrane potential, and activation of mitochondrial apoptotic pathways involving Bax, Bcl-2, and Caspase-3. Isoamyl-p-methoxycinnamate disrupts intracellular redox balance by inhibiting antioxidant enzymes such as catalase, glutathione peroxidase, and superoxide dismutase, while increasing markers of oxidative stress such as malondialdehyde and lactate dehydrogenase.

Animal and cell studies indicate that isoamyl-p-methoxycinnamate may disrupt the endocrine system. This filter showed a anti-oestrogenic and anti-androgenic activity in assays in vitro using yeast expressing human oestrogen (ERα) and androgen receptors. Rat studies with octinoxate, a filter with a structure similar to amiloxate, show that it can interfere with the hypothalamic–pituitary–thyroid axis. Although data on isoamyl-p-methoxycinnamate are limited, its structural similarity to octinoxate heightens concern.

Finally, isoamyl-p-methoxycinnamate is recognised as a potential photoallergen. While cases are rare, several studies using photopatch tests have reported allergic or photoallergic reactions linked to amiloxate. In a study of 111 patients with a positive reaction, two cases of photoallergy to this sunscreen filter were recorded, a reaction rate of 1.8%. Although low, this rate indicates a photoallergic risk for isoamyl-p-methoxycinnamate that is not negligible.

What is the environmental impact of isoamyl p-methoxycinnamate?

The chemical UV filters, including isoamyl p-methoxycinnamate, do not remain confined to the skin surface. Once rinsed off during swimming or showering, they disperse into aquatic environments. Several studies and policy initiatives warn of the ecological effects of this contamination in marine environments. One of the most concerning impacts involves coral reefs. Observations have shown a bleaching of corals on contact with certain UV filters, including isoamyl p-methoxycinnamate. This phenomenon indicates extreme cellular stress in corals, compromises their survival, and weakens the entire marine ecosystem. In response to this threat, the State of Hawaii introduced a bill to restrict the use of sun care products containing UV filters deemed harmful to the oceans, including oxybenzone and amiloxate.

The government of Palau has also taken a stance. Since 2018, it has enacted a law banning the use and distribution of sunscreens containing ten chemical substances, including isoamyl p-methoxycinnamate. This regulation carries financial penalties. Retailers who violate it face a US$1,000 fine. This reflects a firm intent to protect aquatic environments. The French Agency for the Safety of Health Products (AFSSAPS) takes a measured stance. It does not endorse or oppose the use of isoamyl p-methoxycinnamate. It remains alert to emerging data.