Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Risk assessment of cyclohexasiloxane D6 in cosmetic products

  • Yeonju Ko (College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University ERICA) ;
  • Donghyeon Lim (College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University ERICA) ;
  • Hyunjoon Choi (College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University ERICA) ;
  • Seongwon Choi (College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University ERICA) ;
  • Shinai Choi (KnA Co., Ltd.) ;
  • Jiyeon Hong (KnA Co., Ltd.) ;
  • Young A. Yoon (KnA Co., Ltd.) ;
  • Hyun Chung (KnA Co., Ltd.) ;
  • Kyung‑Min Lim (College of Pharmacy, Ewha Womans University) ;
  • Kyu‑Bong Kim (College of Pharmacy, Dankook University) ;
  • Joo Young Lee (College of Pharmacy, The Catholic University of Korea) ;
  • Seung Jun Kwack (College of Natural Sciences, Changwon National University) ;
  • Ok‑Nam Bae (College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University ERICA)
  • Received : 2024.01.03
  • Accepted : 2024.03.21
  • Published : 2024.07.15
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Abstract

Dodecamethylcyclohexasiloxane (D6) is a siloxane substance mainly used in cosmetics and personal care products. While octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) were once commonly used in personal care products, their usage has been restricted due to the classification as persistent, bioaccumulative, and toxic (PBT)/very persistent and very bio-accumulative (vPvB) substances. While D6 has emerged as a substitute for D4 and D5, the risk assessment for D6 remains limited compared to the evaluations for D4 and D5. To address this gap, we conducted a comprehensive risk assessment of D6. In this study, we reviewed the toxicity information on D6 and calculated the exposure level to D6, considering the content of D6 in cosmetic products. No observed adverse effect level (NOAEL) of 1500 mg/kg bw/day was established in a repeated dose toxicity study after oral administration to rats. Negative results were found in tests on the ocular and skin irritation, skin sensitization, and genotoxicity of D6. According to the product content of up to 48% of D6 reported in 2012, the Systemic Exposure Dose (SED) was 5.4E-06 to 7.04 mg/kg bw/day for a 60 kg adult using the exposure factors from Korean cosmetic usage. The Margin of Safety was estimated to be between 35.5 and 4.63E+07, posing a potential health risk of D6 according to the maximum concentration and the product type. Further consideration of the potential of D6 as PBT or vPvB is also required.

Keywords

Acknowledgement

This study was cosmetic safety evaluation project conducted by the Korea Cosmetic Industry Institute (KCII) and funded by the Ministry of Health and Welfare

References

  1. Johnson W Jr, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG Jr, Shank RC, Slaga TJ, Snyder PW, Andersen FA (2011) Safety assessment of cyclomethicone, cyclotetrasiloxane, cyclopentasiloxane, cyclohexasiloxane, and cycloheptasiloxane. Int J Toxicol 30:149S-227S. https://doi.org/10.1177/10915 81811 428184
  2. European Chemicals Agency (ECHA) (2019) Annex XV restriction report proposal for a restriction, vol 1
  3. Krestine G, Nielsen E, Ladefoged O (2014) Siloxanes (D3, D4, D5, D6, HMDS). Environmental Project No. 1531 edn. National Food Institute, Technical University of Denmark, The Danish Environmental Protection Agency
  4. Kumari K, Singh A, Marathe D (2023) Cyclic volatile methyl siloxanes (D4, D5, and D6) as the emerging pollutants in environment: environmental distribution, fate, and toxicological assessments. Environ Sci Pollut Res Int. https://doi.org/10.1007/s11356-023-25568-7
  5. Agency California Environmental Protection (2021) Chemicals in hair straightening products background document. Safer Consumer Products Program. Department of Toxic Substances Control, SAFER consumer Products
  6. Rijcken P (1999) Assessment of acute oral toxicity with dodecamethylcyclohexasiloxan in the rat (acute toxic class method). NOTOX project 262575
  7. Pels Rijcken (1999) Assessment of acute dermal toxicity with dodecamethylcyclohexasilosan in the rat. NOTOX Project 262586
  8. Crofoot SD Stanton E, Siddiqui W, Zimmer MA (1990) A 28-day subchronic oral gavage feasibility study of various low molecular weight silicone oligomers in rats. Report No.1990-I0000-35105. Dow Corning
  9. Environment Canada Health Canada (2008) Screening assessment for the challenge. Dodecamethylcyclohexasiloxane (D6). Environment Canada, Health Canada
  10. Brooke D N Crookes M J, Gray D and Robertson, S (2009) Environmental risk assessment report_dodecamethylcyclohexasiloxane. Environment Agency
  11. Siddiqui WH (2005) Combined repeated dose toxicity study with the reproductive/developmental toxicity screening test for dodecamethylcyclohexasiloxane (D6) in Sprague-Dawley rats. HES study number 10054-012. Health and Environmental sciences, Dow Corning
  12. Pels Rijcken (1999) Acute eye irritation/corrosion study with dodecamethylcyclohexasiloxan in the rabbit. NOTOX project 262597
  13. Pels Rijcken (1999) Primary skin irritation/corrosion study with dodecamethylcyclohexasiloxanj in the rabbit (4-hour semiocclusive application). NOTOX project 262608
  14. Pels Rijcken (1999) Assessment of contact hypersensitivity to dodecamethylcyclohexasiloxan in the albino guinea pig (maximisation-test). NOTOX project 262619
  15. Verspeek-Rip CM (1999) Evaluation of the mutagenic activity of dodecamethylcyclohexasiloxan in the Salmonella typhimurium reverse mutation assay and the Escherichia coli reverse mutation assay with independent repeat. NOTOX project 262621
  16. US-EPA (2004) Pharmacokinetics of 14C-D6 in the rt following single oral exposure. DCN 84030000026
  17. US-EPA (2003) Absorption of D6 using the flow-through diffusion cell system for in vitro absorption in human skin. DCN 84030000026
  18. The Ministry of Food and Drug Safety (MFDS) (2017) Guideline for risk assessment of cosmetic
  19. Tran TM, Tu MB, Vu ND (2018) Cyclic siloxanes in indoor environments from hair salons in Hanoi, Vietnam: emission sources, spatial distribution, and implications for human exposure. Chemosphere 212:330-336. https://doi.org/10.1016/j.chemosphere.2018.08.101
  20. Capela D, Alves A, Homem V, Santos L (2016) From the shop to the drain-Volatile methylsiloxanes in cosmetics and personal care products. Environ Int 92-93:50-62. https://doi.org/10.1016/j.envint. 2016. 03. 016
  21. Scientific Committee on Consumer Safety (SCCS) (2021) The SCCS notes of guidance for the testing of cosmetic ingredients and their safety evaluation 11th revision
  22. Scientific Committee on Consumer Safety (SCCS) (2010) Opinion on cyclomethicone octamethylcyclotetrasiloxane (cyclotetrasiloxane, D4) and decamethylcyclopentasiloxane (cyclopentasiloxane, D5). SCCS/1241/10 edn. https://doi.org/10.2772/24205
  23. Scientific Committee on Consumer Safety (SCCS) (2016) Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products. SCCS/1549/15 edn. https://doi.org/10.2875/841314
  24. Krenczkowska D, Mojsiewicz-Pienkowska K, Wielgomas B, Bazar D, Jankowski Z (2020) Ex vivo human skin is not a barrier for cyclic siloxanes (Cyclic Silicones): evidence of diffusion, bioaccumulation, and risk of dermal absorption using a new validated GC-FID procedure. Pharmaceutics. https://doi.org/10.3390/pharmaceutics12060586
  25. Government of Canada (2023) Siloxane D6 (cyclohexasiloxane, dodecamethyl-) - information sheet