Ethyl 2-cyano-3,3-diphenylacrylate: Safety in Cosmetics, Microbial Transformation and Bioremediation Potential

Ethyl 2-cyano-3,3-diphenylacrylate is an organic ester that appears as an off-white crystalline powder and functions as a UV absorber. When applied to the skin, this product absorbs UV rays. It can also be used to protect cosmetics and personal care products from deterioration. This product can be used in the formulation of sun protection products, as well as bath, skin, cleansing, hair, nail and fragrance products.

The safety of Ethyl 2-cyano-3,3-diphenylacrylate used as an ultraviolet filter in cosmetics

Ethyl 2-cyano-3,3-diphenylacrylate or octocrilene is an organic ultraviolet (UV) filter which absorbs mainly UVB radiation and short UVA wavelengths. It is used in various cosmetic products to either provide an appropriate sun protection factor in sunscreen products or to protect cosmetic formulations from UV radiation. There is no discussion that UV filters are beneficial ingredients in cosmetics since they protect from skin cancer, but  Ethyl 2-cyano-3,3-diphenylacrylate has been recently incriminated to potentially induce adverse effects on the endocrine system in addition to having allergic and/or photoallergic potential. However, the substance has the advantage to work synergistically with other filters allowing a beneficial broad photoprotection, e.g. it stabilizes the UVA filter avobenzone (i.e. butylmethoxydibenzoylmethane). Like all chemicals used in cosmetics, the safety profile of  Ethyl 2-cyano-3,3-diphenylacrylate is constantly under assessment by the European Chemical Agency (ECHA) since it has been registered according to the European regulation Registration, Evaluation, Authorisation and Restriction of Chemicals. Summaries of safety data of  Ethyl 2-cyano-3,3-diphenylacrylate are publicly available on the ECHA website. This review aims to present the main safety data from the ECHA website, as well as those reported in scientific articles from peer-reviewed journals. The available data show that  Ethyl 2-cyano-3,3-diphenylacrylate does not have any endocrine disruption potential. It is a rare sensitizer, photocontact allergy is more frequent and it is considered consecutive to photosensitization to ketoprofen. Based on these results,  Ethyl 2-cyano-3,3-diphenylacrylate can be considered as safe when used as a UV filter in cosmetic products at a concentration up to 10%.[1]

Ethyl 2-cyano-3,3-diphenylacrylate or octocrilene (CAS n. 6197-30-4) is an organic compound with an aromatic structure which is also known as 2-ethylhexyl 2-cyano-3,3-diphenyl-2-propenoate; 2-ethylhexyl 2-cyano-3,3-diphenylacrylate or the 2-ethylhexyl ester of 2-cyano-3,3-diphenyl acrylic acid.It is an organic ultraviolet (UV) filter, which absorbs mainly UVB radiation and short UVA wavelengths. Due to its UV radiation absorption properties, it is used in sunscreens with other UV filters to provide an adequate sun protection factor (SPF). It is also used to stabilize other UV filters such as avobenzone, a filter particularly effective against UVA; this association thus provides an optimal UV protection. Various cosmetic products such as facial creams or lip care products contain  Ethyl 2-cyano-3,3-diphenylacrylate to either provide an adequate SPF or to protect the cosmetic formulation from UV radiation. In Europe, UV filters allowed in cosmetic products are regulated in Annex VI of Cosmetics Regulation (EC) No. 1223/2009. According to this regulation,  Ethyl 2-cyano-3,3-diphenylacrylate is authorized as a UV filter in cosmetic formulations at a maximum concentration of 10.0% as acid form in Europe (Annex VI/10). Of note,  Ethyl 2-cyano-3,3-diphenylacrylate is also authorized as a UV filter in sunscreen products in the same conditions in the USA. The objective of the present document is therefore to evaluate the safety of  Ethyl 2-cyano-3,3-diphenylacrylate on the basis of the publicly available safety data from scientific literature and safety agencies. studies carried out by the manufacturers at the request of safety agencies.

Although the mechanism for the co-reactivity of  Ethyl 2-cyano-3,3-diphenylacrylate and ketoprofen is not yet elucidated, de Groot et al. ventured several hypotheses: (i) the benzophenone moiety in the chemical structure of ketoprofen may be responsible for photoallergy attributed to ketoprofen. Although the benzophenone moiety is not part of the  Ethyl 2-cyano-3,3-diphenylacrylate structure, aminolysis and hydrolysis of  Ethyl 2-cyano-3,3-diphenylacrylate in the skin may result in the formation of benzophenone which then can lead to cross-reactivity. However, at present, it cannot be definitively stated whether or not the reactions are attributable to cross-sensitization; (ii) some people may be hyper-photosusceptible to substances that are non-relevant allergens; (iii) co-reactivity – i.e. concomitant sensitization or prior or subsequent de novo photosensitization – may be involved in place of cross-reaction. The recent study of Romita et al. showed a decreasing trend in photocontact allergy attributed to  Ethyl 2-cyano-3,3-diphenylacrylate from 2014 to 2017, which could not be explained by a restricted use of topical ketoprofen at a European level, as allergy to ketoprofen is still high in their study. Aerts et al. hypothesized that the presence of sensitizing impurities in some commercial batches of  Ethyl 2-cyano-3,3-diphenylacrylate could be the real allergen. The authors also suggested that recent commercial patch tests, more purified than before, might produce false negative reactions and underestimate the prevalence of photoallergy cases.

Microbial biofilm formation and degradation of  Ethyl 2-cyano-3,3-diphenylacrylate

Ethyl 2-cyano-3,3-diphenylacrylate is a widely used synthetic UV absorber of sunscreens and found in several environments. Ecological consequences of the accumulation of UV filters are widely discussed. This is the first report revealing the microbial potential to transform octocrylene. A microbial community comprising four bacterial species was enriched from a landfill site using octocrylene as carbon source. From these microorganisms Mycobacterium agri and Gordonia cholesterolivorans were identified as most potent applying a new “reverse discovery” approach. This relies on the possibility that efficient strains that are already isolated and deposited can be identified through enrichment cultures. These strains formed massive biofilms on the octocrylene droplets. GC-MS analysis after cultivation for 10 days with M. agri revealed a decrease in Ethyl 2-cyano-3,3-diphenylacrylate concentration of 19.1%. LC-MS/MS analysis was utilized in the detection and quantification of transformation products of octocrylene. M. agri thus represents an ideal candidate for bioremediation studies with octocrylene and related compounds.[2]

LC-MS/MS revealed the occurrence of DOCCA with 165 ± 60 µg/L, of CPAA with 11.8 ± 2.6 µg/L and of 5OH-OC with 246.0 ± 34 µg/L. This indicates that M. agri has transformed Ethyl 2-cyano-3,3-diphenylacrylate to the respective metabolites. The concentration of the detectable metabolites, however, does not correlate with the reduction in octocrylene concentration. It is very likely that the products formed in the medium by M. agri (DOCCA, CPAA, and unknown metabolites) were further metabolized by the microorganism and utilized for growth. Non-biotic factors responsible for the reduction of octocrylene can be excluded, since controls without M. agri did not show any decrease in octocrylene concentration.

Since UV filters such as Ethyl 2-cyano-3,3-diphenylacrylate accumulate in nature, the identification of further octocrylene degrading microorganisms is desirable. It has been reported that marine environments are endangered by chemicals and UV-filters of sunscreen and solutions for this pollution have to be investigated. Man-made biofilms were proposed previously for bioremediation of sewage effluent contaminated with hydrocarbons. M. agri represents a potential candidate for bioremediation, since it belongs to the rapidly growing Mycobacteria and can be found ubiquitously in soil and water systems. Therefore, a novel eco-friendly application using M. agri or specific microbial consortia could be investigated and applied for degradation of chemical UV filter like octocrylene. This work highlights the potential of heterotrophic microorganisms to transform Ethyl 2-cyano-3,3-diphenylacrylate in lab experiments. Due to the omnipresence of M. agri in the environment, it is conceivable that M. agri will also be able to transform the UV filter octocrylene in nature. Hence, further analysis should be conducted regarding biotransformation of octocrylene by microorganisms in natural sediments and waters. Future studies will reveal the metabolic pathway for Ethyl 2-cyano-3,3-diphenylacrylate degradation and the key enzymes involved in this process.

References

[1]Berardesca, E et al. “Review of the safety of octocrylene used as an ultraviolet filter in cosmetics.” Journal of the European Academy of Dermatology and Venereology : JEADV vol. 33 Suppl 7 (2019): 25-33.

[2]Suleiman M, Schröder C, Kuhn M, Simon A, Stahl A, Frerichs H, Antranikian G. Microbial biofilm formation and degradation of octocrylene, a UV absorber found in sunscreen. Commun Biol. 2019 Nov 22;2:430.