EVALUATION OF PHOTOTOXIC (PHOTOIRRITANT) AND PHOTOALLERGIC EFFECTS OF FRAGRANCE MATERIALS

Yıl 2025, Cilt: 49 Sayı: 1, 211 - 227, 20.01.2025

Gökçe Durmuş , Irem Ozkan , Ozge Ulker

https://doi.org/10.33483/jfpau.1517163

Öz

Objective: Fragrance components are often included in perfumes, household cleaning products, personal care and cosmetic products today. There are some studies that showed these components led to phototoxicity and photoallergy as a result of sunlight exposure. For this reason, the safety assessment of fragrance components is of great importance. The safety evaluation of the fragrance components is carried out by various tests and methods, they are examined by the relevant organizations. In this review, the risk assessment processes of fragrance components, phototoxicity (photoiritation) and photoallergy reactions, mechanisms caused by sunlight exposure and test methods used to evaluate these negative reactions are summarized. In addition, the safety evaluations of the fragrance components most commonly used in formulations were examined, and the results in terms of phototoxicity and photoallergenicity were also mentioned.
Result and Discussion: The preliminary identification of the components that cause phototoxicity and photoallergy reactions is very important in the production processes and product development stages. Also, having information about these types of components allows consumers to make informed product choices to protect skin health.

Anahtar Kelimeler

Fragrance materials, phototoxicity, photoallergy, safety assessment

KOKU BİLEŞENLERİNİN FOTOTOKSİK (FOTOİRİTAN) VE FOTOALERJİK ETKİLERİNİN DEĞERLENDİRİLMESİ

Öz

Amaç: Koku bileşenleri günümüzde parfümlerde, ev temizliği ürünlerinde, kişisel bakım ve kozmetik ürünlerinde sıklıkla yer almaktadır. Amaçları güzel koku vermek veya kötü kokuları maskelemek olan bu bileşenlerin, güneş ışığına maruziyet sonucu fototoksisite ve fotoalerji gibi çeşitli olumsuz reaksiyonlara sebep olduğu görülebilmektedir. Bu sebeple formülasyonlardaki diğer maddelerde olduğu gibi koku bileşenlerinde de güvenlilik değerlendirmesi oldukça önem arz etmektedir. Çeşitli test ve yöntemlerle koku bileşenlerinin güvenlilik değerlendirmesi yapılmakta, ilgili kuruluşlar tarafından incelenmekte ve kullanım onayı verilmektedir. Bu derlemede koku bileşenlerinin risk değerlendirme prosesleri, güneş ışığına maruziyet sonucu meydana gelen fototoksisite (fotoiritasyon) ve fotoalerji reaksiyonları ve mekanizmaları, bu olumsuz reaksiyonları değerlendirmek için kullanılan test metodları özetlenmiştir. Ayrıca formülasyonlarda en sık kullanılan koku bileşenlerinin güvenlilik değerlendirmeleri incelenmiş, fototoksisite ve fotoalerji açısından sonuçlarına değinilmiştir.
Sonuç ve Tartışma: Fototoksisite ve fotoalerji reaksiyonlarına neden olan bileşenlerin önceden tespit edilmesi, üretim süreçlerinde ve ürün geliştirme aşamalarında oldukça önemlidir ayrıca bu tip bileşenler hakkında bilgi sahibi olmak, tüketicilerin cilt sağlığını korumak için bilinçli ürün seçimine olanak sağlar.

Anahtar Kelimeler

Fotoalerji, fototoksisite, güvenlilik değerlendirmesi, koku bileşenleri

Kaynakça

• 1. Api, A.M., Belsito, D., Bruze, M., Cadby, P., Calow, P., Dagli, M.L., Dekant, W., Ellis, G., Fryer, A.D., Fukayama, M., Griem, P., Hickey, C., Kromidas, L., Lalko, J.F., Liebler, D.C., Miyachi, Y., Politano, V. T., Renskers, K., Ritacco, G., Salvito, D., Schultz, T.W., Sipes, I.G., Smith, B., Vitale, D., Wilcox, D.K. (2015). Criteria for the Research Institute for Fragrance Materials, Inc. (RIFM) safety evaluation process for fragrance ingredients. Food and Chemical Toxicology, 82(S), 1-19. [CrossRef]
• 2. Scientific Committee on Consumer Safety. (2012). Opinion on fragrance allergens in cosmetic products. Scientific Committee on Consumer Safety, 1459(11), 2-334. Retrieved December 9, 2024, from https://ec.europa.eu/health/scientific_committees/. Erişim Tarihi: 6 Haziran 2024.
• 3. Bickers, D.R., Calow, P., Greim, H.A., Hanifin, J.M., Rogers, A.E., Saurat, J.H., Sipes, I.G., Smith, R.L., Tagami, H. (2003). The safety assessment of fragrance materials. Regulatory Toxicology and Pharmacology, 37(2), 218-273. [CrossRef]
• 4. ECHA (European Chemicals Agency) Web site. (2024). From https://echa.europa.eu/support/ substance-identification/what-is-a-substance. Erişim Tarihi: 6 Haziran 2024.
• 5. Api, A.M., Belsito, D., Biserta, S., Botelho, D., Bruze, M., Burton, G.A., Buschmann, J., Cancellieri, M. A., Dagli, M.L., Date, M., Dekant, W., Deodhar, C., Fryer, A.D., Gadhia, S., Jones, L., Joshi, K., Lapczynski, A., Lavelle, M., Liebler, D.C., Tsang, S. (2021). RIFM low-exposure fragrance ingredients safety assessment. Food and Chemical Toxicology, 149, 111981. [CrossRef]
• 6. CDER, FDA. (2015). International Conference on Harmonisation; S10 Photosafety Evaluation of Pharmaceuticals; guidance for industry; availability. Notice. Federal Register, 80(17), 4282-4283.
• 7. Harrison, T.J., Chen, X., Yasoshima, K., Bauer, D. (2023). Phototoxicity-medicinal chemistry strategies for risk mitigation in drug discovery. Journal of Medicinal Chemistry, 66(14), 9345-9362. [CrossRef]
• 8. Türkiye İlaç ve Tıbbi Cihaz Kurumu (TİTCK). (2021). Kozmetik Ürünlerde Güvenlilik Değerlendirmesine İlişkin Kılavuz Sürüm 3.0 Amaç. Gastronomía Ecuatoriana y Turismo Local., 1(69), 5-24. Retrieved August 13, 2024, from https://titck.gov.tr/storage/Archive/2024/. Erişim Tarihi: 6 Haziran 2024.
• 9. Kroes, R., Kleiner, J., Renwick, A. (2005). The threshold of toxicological concern concept in risk assessment. Toxicological Sciences, 86(2), 226-230. [CrossRef]
• 10. Kim, K., Park, H., Lim, K.M. (2015). Phototoxicity: Its mechanism and animal alternative test methods. Toxicological Research, 31(2), 97-104. [CrossRef]
• 11. Köse, Ö., Erkekoğlu, P., Sabuncuoğlu, S., Koçer-Gümüşel, B. (2017). Kozmetik ürünlerin fototoksik etkileri: Mekanizması ve alternatif test metotları. Marmara Pharmaceutical Journal, 21(2), 202-210. [CrossRef]
• 12. Food and Drug Administration Web site. (2020). From https://www.fda.gov/radiation-emitting-products/tanning/ultraviolet-uv-radiation. Erişim Tarihi: 30 Mayıs 2024.
• 13. Maibach, H.I., Marzulli, F.N. (1986). Photoirritation (Phototoxicity) from topical agents. Dermatologic Clinics, 4(2), 217-222. [CrossRef]
• 14. Lozzi, F., Di Raimondo, C., Lanna, C., Diluvio, L., Mazzilli, S., Garofalo, V., Dika, E., Dellambra, E., Coniglione, F., Bianchi, L., Campione, E. (2020). Latest evidence regarding the effects of photosensitive drugs on the skin: Pathogenetic mechanisms and clinical manifestations. Pharmaceutics, 12(11), 1-17. [CrossRef]
• 15. Di Bartolomeo, L., Irrera, N., Campo, G.M., Borgia, F., Motolese, A., Vaccaro, F., Squadrito, F., Altavilla, D., Condorelli, A.G., Motolese, A., Vaccaro, M. (2022). Drug-induced photosensitivity: Clinical types of phototoxicity and photoallergy and pathogenetic mechanisms. Frontiers in Allergy, 3(June), 1-8. [CrossRef]
• 16. Guan, L.L., Lim, H.W., Mohammad, T.F. (2022). Recognizing photoallergy, phototoxicity, and immune-mediated photodermatoses. Journal of Allergy and Clinical Immunology, 149(4), 1206-1209. [CrossRef]
• 17. Tønnesen, H.H. (2001). Formulation and stability testing of photolabile drugs. International Journal of Pharmaceutics, 225(1-2), 1-14. [CrossRef]
• 18. Tenenbaum, S., DiNardo, J., Morris, W.E., Wolf, B.A., Schnetzinger, R.W. (1984). A quantitative in vitro assay for the evaluation of phototoxic potential of topically applied materials. Cell Biology and Toxicology, 1(1), 1-9. [CrossRef]
• 19. Placzek, M., Frömel, W., Eberlein, B., Gilbertz, K., Przybilla, B. (2007). Evaluation of phototoxic properties of fragrances. Acta Dermato-Venereologica, 87(4), 312-316. [CrossRef]
• 20. Epstein, J.H. (1999). Phototoxicity and photoallergy. Seminars in Cutaneous Medicine and Surgery, 18(4), 274-284. [CrossRef]
• 21. Seto, Y., Hosoi, K., Takagi, H., Nakamura, K., Kojima, H., Yamada, S., Onoue, S. (2012). Exploratory and regulatory assessments on photosafety of new drug entities. Current Drug Safety, 7(2), 140-148. [CrossRef]
• 22. OECD. (2019). Test Guideline No. 432 In Vitro 3T3 NRU Phototoxicity Test. Retrieved May 13, 2024, from https://www.oecd.org/content/dam/oecd/en/publications/reports/2019/06/. Erişim Tarihi: 6 Haziran 2024.
• 23. Infante, V.H.P., Maia Campos, P.M.B.G., Gaspar, L.R., Darvin, M.E., Schleusener, J., Rangel, K.C., Meinke, M.C., Lademann, J. (2022). Safety and efficacy of combined essential oils for the skin barrier properties: In vitro, ex vivo and clinical studies. International Journal of Cosmetic Science, 44(1), 118-130. [CrossRef]
• 24. Nishida, H., Hirota, M., Seto, Y., Suzuki, G., Kato, M., Kitagaki, M., Sugiyama, M., Kouzuki, H., Onoue, S. (2015). Non-animal photosafety screening for complex cosmetic ingredients with photochemical and photobiochemical assessment tools. Regulatory Toxicology and Pharmacology, 72(3), 578-585. [CrossRef]
• 25. Pape, W.J., Maurer, T., Pfannenbecker, U., Steiling, W. (2001). The red blood cell phototoxicity test (photohaemolysis and haemoglobin oxidation): EU/COLIPA validation programme on phototoxicity (Phase II). ATLA. Alternatives to Laboratory Animals, 29(2), 145-162. [CrossRef]
• 26. Api, A.M., Belsito, D., Botelho, D., Bruze, M., Burton, G.A., Buschmann, J., Cancellieri, M.A., Dagli, M. L., Date, M., Dekant, W., Deodhar, C., Fryer, A.D., Jones, L., Joshi, K., Kumar, M., Lapczynski, A., Lavelle, M., Lee, I., Liebler, D.C., Tokura, Y. (2022). Update to RIFM fragrance ingredient safety assessment, eugenol, CAS Registry Number 97-53-0. Food and Chemical Toxicology, 163(April), 113027. [CrossRef]
• 27. Api, A.M., Belsito, D., Bhatia, S., Bruze, M., Calow, P., Dagli, M.L., Dekant, W., Fryer, A.D., Kromidas, L., La Cava, S., Lalko, J.F., Lapczynski, A., Liebler, D.C., Miyachi, Y., Politano, V.T., Ritacco, G., Salvito, D., Schultz, T.W., Shen, J., Wilcox, D.K. (2016a). RIFM fragrance ingredient safety assessment, Eugenol, CAS Registry Number 97-53-0. Food and Chemical Toxicology, 97, 25-37. [CrossRef]
• 28. Api, A.M., Belsito, D., Botelho, D., Bruze, M., Burton, G.A., Buschmann, J., Cancellieri, M.A., Dagli, M. L., Date, M., Dekant, W., Deodhar, C., Fryer, A.D., Jones, L., Joshi, K., Kumar, M., Lapczynski, A., Lavelle, M., Lee, I., Liebler, D.C., Tokura, Y. (2022). RIFM fragrance ingredient safety assessment, hydroxycitronellal, CAS Registry Number 107-75-5. Food and Chemical Toxicology, 163, 1-12. [CrossRef]
• 29. Api, A.M., Belsito, D., Botelho, D., Bruze, M., Burton, G.A., Cancellieri, M.A., Chon, H., Dagli, M.L., Date, M., Dekant, W., Deodhar, C., Fryer, A.D., Jones, L., Joshi, K., Kumar, M., Lapczynski, A., Lavelle, M., Lee, I., Liebler, D.C., Tokura, Y. (2022). RIFM fragrance ingredient safety assessment, geraniol, CAS registry number 106-24-1. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, 167, 113341. [CrossRef]
• 30. Lapczynski, A., Bhatia, S.P., Foxenberg, R.J., Letizia, C.S., Api, A.M. (2008). Fragrance material review on geraniol. Food and Chemical Toxicology, 46(11), 160-170. [CrossRef]
• 31. Api, A.M., Belsito, D., Bhatia, S., Bruze, M., Calow, P., Dagli, M.L., Dekant, W., Fryer, A.D., Kromidas, L., La Cava, S., Lalko, J F., Lapczynski, A., Liebler, D.C., Miyachi, Y., Politano, V.T., Ritacco, G., Salvito, D., Schultz, T.W., Shen, J., Wilcox, D.K. (2016). RIFM fragrance ingredient safety assessment, isoeugenol, CAS Registry Number 97-54-1. Food and Chemical Toxicology, 97, 49-56. [CrossRef]
• 32. Api, A.M., Belsito, D., Bhatia, S., Bruze, M., Calow, P., Dagli, M.L., Dekant, W., Fryer, A.D., Kromidas, L., La Cava, S., Lalko, J.F., Lapczynski, A., Liebler, D.C., Miyachi, Y., Politano, V.T., Ritacco, G., Salvito, D., Shen, J., Schultz, T.W., Wilcox, D.K. (2015). RIFM fragrance ingredient safety assessment, α-amylcinnamaldehyde, CAS registry number 122-40-7. Food and Chemical Toxicology, 82(S), 20-28. [CrossRef]
• 33. Bickers, D., Calow, P., Greim, H., Hanifin, J.M., Rogers, A.E., Saurat, J.H., Sipes, I.G., Smith, R.L., Tagami, H., RIFM expert panel (2005). A toxicologic and dermatologic assessment of cinnamyl alcohol, cinnamaldehyde and cinnamic acid when used as fragrance ingredients. Food and Chemical Toxicology, 43(6), 799-836. [CrossRef]
• 34. Tisserand, R., Young R. (1995). Essential oil Safety: A guide for health care professionals. Elsevier, Amsterdam, p. 97-98.
• 35. Erdogan Eliuz, E.A., Ayas, D., Goksen, G. (2017). In vitro phototoxicity and antimicrobial activity of volatile oil obtained from some aromatic plants. Journal of Essential Oil-Bearing Plants, 20(3), 758-768. [CrossRef]
• 36. Api, A., Belsito, D., Botelho, D., Bruze, M., Burton, G., Buschmann, J., Cancellieri, M., Dagli, M., Date, M., Dekant, W., Deodhar, C., Fryer, A., Jones, L., Joshi, K., Kumar, M., Lapczynski, A., Lavelle, M., Lee, I., Liebler, D., Tokura, Y. (2021). RIFM fragrance ingredient safety assessment, vanillyl butyl ether, CAS Registry Number 82654-98-6. Food and Chemical Toxicology, 153, 112361. [CrossRef]
• 37. Cosmetic Ingredient Safety. (2020). Safety Assessment of Vanilla-Derived Ingredients as Used in Cosmetics, 36. Retrieved June 25, 2024 from https://www.cir-safety.org/sites/. Erişim Tarihi: 6 Haziran 2024.
• 38. Api, A., Belsito, D., Botelho, D., Browne, D., Bruze, M., Burton, G., Buschmann, J., Dagli, M., Date, M., Dekant, W., Deodhar, C., Francis, M., Fryer, A., Joshi, K., La Cava, S., Lapczynski, A., Liebler, D., O’Brien, D., Parakhia, R., Wahler, J. (2017). RIFM fragrance ingredient safety assessment, menthyl acetate (isomer unspecified), CAS Registry Number 16409-45-3. Food and Chemical Toxicology, 110, 619-628. [CrossRef]
• 39. Nair, B. (2001). Final Report on the safety assessment of Mentha piperita (Peppermint) oil, Mentha piperita (Peppermint) leaf extract, Mentha piperita (Peppermint) leaf, and Mentha piperita (Peppermint) leaf water. International Journal of Toxicology, 20(3), 61-73. [CrossRef]
• 40. Guin, J.D., Jackson, D.B. (1988). Oakmoss photosensitivity in a ragweed-allergic patient. Contact dermatitis, 18(4), 240-242. [CrossRef]
• 41. Burdock, G.A., Carabin, I.G. (2008). Safety assessment of Ylang-Ylang (Cananga spp.) as a food ingredient. Food and Chemical Toxicology, 46(2), 433-445. [CrossRef]
• 42. Kejlová, K., Jírová, D., Bendová, H., Kandárová, H., Weidenhoffer, Z., Kolářová, H., Liebsch, M. (2007). Phototoxicity of bergamot oil assessed by in vitro techniques in combination with human patch tests. Toxicology In Vitro, 21(7), 1298-1303. [CrossRef]
• 43. Zaynoun, S.T., Johnson, B.E., Frain-Bell, W. (1977). A study of oil of bergamot and its importance as a phototoxic agent. II. Factors which affect the phototoxic reaction induced by bergamot oil and psoralen derivatives. Contact Dermatitis, 3(5), 225-239. [CrossRef]
• 44. Türkiye İlaç ve Tıbbi Cihaz Kurumu (TİTCK). (2017). Beşeri Tıbbi Ürünlerin Ambalaj Bilgileri ve Kullanma Talimatına İlişkin Kılavuz, Beşeri Tıbbi Ürünlerin Ambalaj Bilgileri ve Kullanma Talimatının Okunabilirliğine İlişkin Kılavuz ve Beşeri Tıbbi Ürünlerin Ambalaj Bilgileri ve Kullanma Talimatındaki Yardımcı Maddelere İlişkin Kılavuz, 33. Retrieved June 11, 2024, from https://titck.gov.tr/storage/Archive/2024/. Erişim Tarihi: 6 Haziran 2024.
• 45. Scientific Committee on Consumer Safety. (2012). Opinion on hydroxyisohexyl 3-cyclohexene carboxaldehyde (sensitisation only). Retrieved June 27, 2024, from https://ec.europa.eu/health/scientific_committees/. Erişim Tarihi: 6 Haziran 2024.
• 46. Eun, H.C., An, S., Lee, H., Lee, A., Lee, C.H., Kim, D.W., Moon K, Won Y., Ro, Y., Hahm, J., Kim, K.J. (2004). FS14. 1 Safety of various fragrances: Allergy and phototoxicity, joint study in Korea. Contact Dermatitis, 50(3), 174-175. [CrossRef]
• 47. Tenenbaum, S., DiNardo, J., Morris, W.E., Wolf, B.A., Schnetzinger, R.W. (1984). A quantitative in vitro assay for the evaluation of phototoxic potential of topically applied materials. Cell Biology Toxicology, 1(1),1-9. [CrossRef]
• 48. Bickers, D., Calow, P., Greim, H., Hanifin, J.M., Rogers, A.E., Saurat, J.H., Sipesg, I.G., Smithh, R.L, Tagami, H. (2003). A toxicologic and dermatologic assessment of linalool and related esters when used as fragrance ingredients. Food and Chemical Toxicology, 41(7), 919-942. [CrossRef]
• 49. Hotchkiss, S.A.M., Miller, J.M., Caldwell, J. (1992). Percutaneous absorption of benzyl acetate through rat skin in vitro. 2. Effect of vehicle and occlusion. Food and Chemical Toxicology, 30(2), 145-153. [CrossRef]
• 50. Ford, R.A., Hawkins, D.R., Mayo, B.C., Api, A.M. (2001). The in vivo dermal absorption and metabolism of [4-14C] coumarin by rats and by human volunteers under simulated conditions of use in fragrances. Food and Chemical Toxicology, 39(2), 153-162. [CrossRef]
• 51. Ahlström, M.G., Uter, W., Ahlström, M.G., Johansen, J.D. (2021). Decrease of contact allergy to hydroxyisohexyl 3‐cyclohexene carboxaldehyde in Europe prior to its ban and diagnostic value. Contact Dermatitis, 84(6), 419-422. [CrossRef]