DOI QR코드

DOI QR Code

Characteristics of Percutaneous Absorption for Three Kinds of Phthalate

Phthalate 3종에 대한 경피투과 특성 연구

  • Received : 2013.06.07
  • Accepted : 2013.08.07
  • Published : 2013.08.31

Abstract

Objectives: Phthalates are used in a large variety of products including as coatings of pharmaceutical tablets, film formers, stabilizers, dispersants, emulsifying agents, and suspending agents. They have been the subject of great public concern in recent years. The extensive uses of this material have attracted attention and issues regarding its safety have been raised. Methods: In this study, three types of phthalate skin permeation were studied using matrixes such as ointments, creams and lotions in vitro. The absorption of phthalate diesters [Dimethyl phthalate (DMP), Di-n-propyl phthalate (DPP) and Di-n-pentyl phthalate (DNPP)] using film former has been measured in vitro through rat skin. Epidermal membranes were set up in Franz diffusion cells and their permeability to PBS measured in order to establish the integrity of the skin before the phthalates were applied to the epidermal surface. Results: Absorption rates for each phthalate ester were determined and permeability assessment made to quantify any irreversible alterations in barrier function due to contact with the esters. Types of phthalate in vitro experimental results quickly appeared in the following order DMP > DPP ${\geq}$ DNPP. Conclusions: In the experimental results, lotion> cream> ointment, and the permeation rate of lotion with a great amount of moisture was the fastest. Skin permeation rate is generally influenced by the chemical characteristics of a given chemical, such as molecular weight and lipophilicity. As the esters became more lipophilic and less hydrophilic, the rate of absorption decreased.

Keywords

References

  1. Rudel R, Perovich L. Endocrine disrupting chemicals in indoor and outdoor air. Atmos Environ. 2008; 43(1): 170-81.
  2. Gray LE, Ostby J, Furr J, Price M, Veeramachaneni DN, Parks L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci. 2000; 58(2): 350-65. https://doi.org/10.1093/toxsci/58.2.350
  3. Mendes F, Amaral J. The endocrine disruptors: a major medical challenge. Food Chem Toxicol. 2002; 40(6): 781-788. https://doi.org/10.1016/S0278-6915(02)00018-2
  4. Latini G, Del Vecchio A, Massaro M, Verrotti A, De Felice C. Phthalate Exposure and Male Infertility. Toxicology. 2006; 226(2-3): 90-98. https://doi.org/10.1016/j.tox.2006.07.011
  5. Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, Calafat AM. DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod. 2007; 22(3): 688-95. https://doi.org/10.1093/humrep/del428
  6. Barr DB, Silva MJ, Kato K, Reidy JA, Mal NA, Hurtz D. Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers. Environ. Health Perspect. 2003; 111(9): 1148-1151. https://doi.org/10.1289/ehp.6074
  7. Mickelsen RL, Hall RC, Chern RT, Myers JR. Evaluation of a simple weight-loss method for determining the permeation of organic liquids through rubber films. Am Ind Hyg Assoc J. 1991; 52(10): 445-447. https://doi.org/10.1080/15298669191365018
  8. Riviere JE, Brooks JD. Predicting skin permeability from complex chemical mixtures. Toxicol Appl Pharmacol. 2005; 208(2): 99-110. https://doi.org/10.1016/j.taap.2005.02.016
  9. Brain KR, Walters KA, Green DM, Brain S, Loretz LJ, Sharma RK. Percutaneous penetration of diethanolamine through human skin in vitro: application from cosmetic vehicles. Food Chem Toxicol. 2005; 43(5): 681-90. https://doi.org/10.1016/j.fct.2004.12.021
  10. Pappinen S, Tikkinen S, Pasonen-Seppanen S, Murtomaki L, Suhonen M, Urtti A. Rat epidermal keratinocyte organotypic culture (ROC) compared to human cadaver skin: The effect of skin permeation enhancers. Eur J Pharm Sci. 2007; 30(3-4): 240-250. https://doi.org/10.1016/j.ejps.2006.11.013
  11. Anissimov YG , Roberts MS. Diffusion modeling of percutaneous absorption kinetics. 2. Finite vehicle volume and solvent deposited solids. J Pharm Sci. 2001; 90(4): 504-520. https://doi.org/10.1002/1520-6017(200104)90:4<504::AID-JPS1008>3.0.CO;2-H
  12. McCarley KD, Bunge AL. Review of pharmacokinetic models of dermal absorption. J Pharm Sci. 2001; 90(11): 1699-1719. https://doi.org/10.1002/jps.1120
  13. Clowes HM, Scott RC, Heylings JR. Skin absorption: flow-through or static diffusion cells. Toxicol In Vitro. 1994; 8(4): 827-30. https://doi.org/10.1016/0887-2333(94)90078-7
  14. OECD. OECD Guidelines for the Testing of Chemicals / Section 4: Health Effects Test No. 428: Skin Absorption: In Vitro Method. Paris:OECD Press; 2004. p.1-8.
  15. OECD. OECD Guidelines for the Testing of Chemicals / Section 4: Health Effects Test No. 427: Skin Absorption: In Vitro Method. Paris: OECD Press; 2004. p.1-8.
  16. Brien O, Richard W, Lee R. Electrophoretic mobility of a spherical colloidal particle. J Chem Soc Faraday Trans 2 1978; 74: 1607-1626. https://doi.org/10.1039/f29787401607
  17. Robert C. Scott, Paul H. Dugard, John D. Ramsey, Christopher Rhodes, In Vitro Absorption of Some o-Phthalate Diesters Through Human and Rat Skin. Environ Health Perspect. 1987; 74: 223-227. https://doi.org/10.1289/ehp.8774223
  18. ATSDS. Agency for Toxic Substances and Disease Registry Safeguarding Communities from Chemical Exposures. Atlanta GA:ATSDA Press; p.1-38.
  19. SCCNFP. The Scientific Committee on Cosmetic Products and Non-food products intended for Consumers. Diethyl Phthalate Press; 2002. p.1-63.
  20. National Toxicology Program National Institute of Environmental Health Sciences National Institutes of Health U.S. Department of Health and Human Services Research Triangle Park, NC. Chemical Information Profile for Diethyl Phthalate, Supporting Nomination for Toxicological Evaluation by the National Toxicology Program. NTP Press; 2006. p.1-16
  21. Lian G, Chen L, Han L. An evaluation of mathematical models for predicting skin permeability. J Pharm Sci. 2008; 97(1): 584-598. https://doi.org/10.1002/jps.21074
  22. Crank J. The Mathematics of Diffusion 2nd ed. London: Clarendon Press; 1995. p.42-61.
  23. Shah JC. Analysis of permeation data : evaluation of the lag time method. Int J Pharm. 1993; 90(2): 161-169. https://doi.org/10.1016/0378-5173(93)90152-6
  24. Gamer AO, Leibold E, van Ravenzwaay B. The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. Toxicol In Vitro. 2006; 20(3): 301-307. https://doi.org/10.1016/j.tiv.2005.08.008
  25. Mavon A, Miquel C, Lejeune O, Payre B, Moretto P. In vitro percutaneous absorption and in vivo stratum corneum distribution of an organic and a mineral sunscreen. Skin Pharmacol Physiol. 2007; 20(1): 10-20. https://doi.org/10.1159/000096167
  26. Pappinen S, Tikkinen S, Pasonen-Seppanen S, Murtomaki L, Suhonen M, Urtti A. Rat epidermal keratinocyte organotypic culture (ROC) compared to human cadaver skin: The effect of skin permeation enhancers. Eur J Pharm Sci. 2007; 30(3-4): 240-250. https://doi.org/10.1016/j.ejps.2006.11.013
  27. Mavon A, Miquel C, Lejeune O, Payre B, Moretto P, In vitro Percutaneous Absorption and in vivo Stratum Corneum Distribution of an Organic and a Mineral Sunscreen, Skin Pharmacol Appl Skin Physiol, 2007; 20(1): 10-20. https://doi.org/10.1159/000096167
  28. Cevc G. Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev. 2004; 56(5): 675-711. https://doi.org/10.1016/j.addr.2003.10.028
  29. Lee CK, Uchida T, Kitagawa K, Yagi A, Kim NS, Goto S. Effect of hydrophilic and lipophilic vehicles on skin permeation of tegafur with and without permeation enhancers. Biol Pharm Bull. 1993; 16(12): 1264-1269. https://doi.org/10.1248/bpb.16.1264
  30. Hwang SK, Oh SY. Percutaneous absorption Characteristics of antihyperlipidemia gel ointment using Fibric acid. J Kor Oil Chem. Soc. 2010; 27(4): 407-414.
  31. Hadgraft J. Modulation of the barrier function of the skin. Skin Pharm Appl Skin Physiol. 2001; 14(1): 72-81. https://doi.org/10.1159/000056393