COMPUTATIONAL ASSESSMENT OF THE ADME-TOX PROFILES AND HARMFUL EFFECTS OF THE MOST COMMON USED PHTHALATES ON THE HUMAN HEALTH
DOI:
https://doi.org/10.24193/subbchem.2019.4.06Keywords:
phthalates, ADME-Tox, pharmacokinetics, toxicological effectsAbstract
In this study, we consider 25 of the most commonly used phthalates and summarize the available data that support their effects on humans. For 15 of the 25 investigated phthalates (60%) there are no human hazard assessment data, neither from experimental nor from computational studies, which underlines the necessity of their risk assessment. Consequently, we have used various computational tools to predict their ADME-Tox profiles and assess their harmful effects on humans. The outcomes of our study reveal that the investigated phthalates have good bioavailability and skin permeability which are associated with toxicity, especially when they are inhaled. They are able to interact with important molecular targets in the human organism such as membrane receptors, cytochromes, kinases, phosphatases, transcription factors, or transporters. These interactions may conduct to predicted harmful effects of phthalates, such as toxicity and irritations of the respiratory and gastrointestinal tracts, skin and eye irritations, endocrine disruption potential, or non-genotoxic carcinogenicity. The investigated phthalates are not predicted to produce genotoxic carcinogenicity, mutagenicity and cardiotoxicity. Beside the investigated phthalates, the di(2-ethylhexyl) phthalate reflects the highest number of toxic effects, and the ditridecyl phthalate and the diisotrodecyl phthalate illustrate the smallest number of possible toxicological effects, namely skin irritation, non-genotoxic carcinogenicity and endocrine disruption potential.
References
R.U. Halden, Annu Rev Public Health, 2010, 31, 179-194.
C. Gennings, R. Hausser, H.M. Koch, A. Kortenkamp, P.J. Lioy, P.E. Mirkes, B.A. Schwetz, Report to the U.S. Consumer Product Safety Commission by the Chronic hazard advisory panel on phthalates and phthalate alternatives, 2014. https://www.cpsc.gov/chap. Accessed 18 January 2019.
R.M. David, R.H. McKee, J.H. Butala, R.A. Barter, M. Kayser, Esters of aromatic mono-, di-, and tricarboxylic acids, aromatic diacids, and di-, tri-, or polyalcohols. In Patty’s toxicology, E. Bingham, B. Cohrssen, C.H. Powell Eds, John Wiley & Sons, New York, USA, 2001, Volume 6. pp. 635.
J. Doull, R. Cattley, C. Elcombe, B.G. Lake, J. Swenberg, C. Wilkinson, G. Williams, van M. Gemert, Regul Toxicol Pharmacol, 1999, 29, 327-357.
M. Wittassek, H.M. Koch, J. Angerer, T. Bruning, Mol Nutr Food Res, 2011, 55, 7-31.
W. Davidson-Urbain, P. Jouvet, M.P. Vélez, P. Ayotte, P. Monnier, Biomed J Sci & Tech Res, 2018, 6, 5124-5129.
National Research Council. Intentional Human Dosing Studies for EPA Regulatory Purposes: Scientific and Ethical Issues, Committee on the Use of Third Party Toxicity Research with Human Research Participants Science, Technology, and Law Program, 2004, http://www.nap.edu/catalog/10927.html. Accessed 20 January 2019.
The National Institute for Occupational Safety and Health (NIOSH). https://www.cdc.gov/niosh/. Accessed between November 2017 – February 2019.
Occupational Safety and Health Administration (OSHA). https://www.osha.gov/. Accessed between November 2017 – June 2017.
Toxicology Data Network (TOXNET). https://toxnet.nlm.nih.gov/newtoxnet/hsdb.htm. Accessed between November 2017 – February 2019.
The PubChem database. https://pubchem.ncbi.nlm.nih.gov/#. Accessed between November 2017 – June 2017.
BIBRA Toxicology Advice & Consulting. https://www.bibra-information.co.uk/toxicity-profiles-overview/. Accessed between November 2017 – February 2019.
D. Oral, P. Erkekoglu, B.K. Gumusel, M.-W. Chao, J Environ Pathol Toxicol Oncol, 2016, 35, 43-58.
R. Hauser, A.M. Calafat, Occup Environ Med, 2005, 62, 806-818.
M.H. Asghari, S. Saeidnia, M. Abdollahi, Int J Pharm, 2015, 11, 95-105.
I. Katsikantami, S. Sifakis, M.N. Tzatzarakis, E. Vakonaki, O.I. Kalantzi, A.M. Tsatsakis, A.K. Rizos, Environ Int, 2016, 97, 212-236.
S.S.S. Rowdhwal, JX. Chen, Hindawi BioMed Research International, 2018, Article ID 1750368.
J. Knez, Reprod Biomed Online, 2013, 26, 440-448.
R. Rozati, P.P. Reddy, P. Reddanna, R. Mujtaba, Fertil Steril, 2002, 78, 1187-1194.
N. Pant, M. Shukla, D. Kumar Patel, Y. Shukla, N. Mathur, Y. Kumar Gupta, D.K. Saxena, Toxicol Appl Pharmacol, 2008, 231, 112-116.
R. Hauser, Int J Androl, 2008, 31,112-117.
L. López-Carrillo, R.U. Hernández-Ramírez, A.M. Calafat, L. Torres-Sánchez, M. Galván-Portillo, L.L. Needham, R. RuizRamos, M.E. Cebrián, Environ Health Perspect, 2010, 118, 539-544.
J.A. Hoppin, R. Ulmer, S.J. London, Environ Health Perspect, 2004, 112, 571-574.
Y.-J. Lien, H.-Y. Ku, P.-H. Su, S.J. Chen, H.Y. Chen, P.C. Liao, W.J. Chen, S.L. Wang, Environ Health Perspect, 2015, 123, 95-100.
C.G. Bornehag, J. Sundell, C.J. Weschler, K.-G. Bornehag, J. Sundell, C.J. Weschler, T. Sigsgaard, B. Lundgren, M. Hasselgren, L. Hägerhed-Engman, Environ Health Perspect, 2004, 112, 1393-1397.
M. Matsumoto, M. Hirata-Koizumi, M. Ema, Regul Toxicol Pharmacol, 2008, 50, 37-49.
L.C. Li, S.L. Wang, Y.C. Chang, P.C. Huang, J.T. Cheng, P.H. Su, P.C. Liao, Chemosphere, 2011, 83, 1192-1199.
A. Araki, T. Mitsui, C. Miyashita, T. Nakajima, H. Naito, S. Ito, S. Sasaki, K. Cho, T. Ikeno, K. Nonomura, R. Kishi, PLoS One, 2014, 9, Article ID e109039.
H.-Y. Ku, P.-H. Su, H.-J. Wen, S.-L. Wang, PLoS One, 2015, 10, e0123309.
R. Rozati, P.P. Reddy, P. Reddanna, R. Mujtaba, Fertil Steril, 2002, 78, 11871194.
S.H. Swan, S. Sathyanarayana, E.S. Barrett, Hum Reprod, 2015, 30, 963-972.
S.H. Kim, S. Chun, J.Y. Jang, H.D. Chae, C.-H. Kim, B.M. Kang, Fertil Steril, 2011, 95, 357-359.
S.H. Kim, S. Cho, H.J. Ihm, Y.S. Oh, S.H. Heo, S. Chun, H. Im, H.D. Chae, C.H. Kim, B.M. Kang, J Clin Endocr Metab, 2015, 100, E1502-E1511.
B. Kolarik, K.Naydenov, M. Larsson, C.G. Bornehag, J. Sundell, Environ Health Perspect, 2008, 116, 98-103.
Y. Wang, S.H. Bryant, T. Cheng, J. Wang, A. Gindulyte, B.A. Shoemaker, P.A. Thiessen, S. He, J. Zhang, Nucleic Acids Res, 2017, 45, D955-D963.
P. Wolkoff, Int J Hyg Environ Health, 2013, 216, 371-394.
M. De Falco, M. Forte, V. Laforgia, Front Environ Sci, 2015, 3, 1-12.
M.A. Kamrin, J Toxicol Environ Health, Part B, 2009, 12, 157-174.
A.B. Raies, V.B. Bajic, Wiley Interdiscip Rev Comput Mol Sci, 2016, 6, 147-172.
C. Lu, C.M. Holbrook, L.M. Andres, Environ Health Perspect, 2010, 118, 125-130.
D. Craciun, D. Modra, A. Isvoran, AIP Conf Proc, 2015, 1694, 040007-1-040007-6.
Y. Gao, T. An, Y. Ji, G. Li, C. Zhao, Environ Pollu, 2015, 206, 510-517.
O.V. Tinkov, L.N. Ognichenko, V.E. Kuzmin, L.G. Gorb, A.P. Kosinskaya, N.N. Muratov, E.N. Muratov, F.C. Hill, J. Leszczynski, Struct Chem, 2016, 27, 191-198.
I.A. Sheikh, R.F. Turki, A.M. Abuzenadah, G.A. Damanhouri, M.A. Beg, PLoS ONE, 2016, 11, Article ID e0151444.
A. Isvoran, A. Ciorsac, V. Ostafe, ADMET & DMPK, 2017, 5, 192-200.
M. Roman, D.L. Roman, V. Ostafe, A. Ciorsac, Pharm Res, 2018, 35, Article ID 41.
M. Roman, D.L. Roman, V. Ostafe, A. Isvoran, J Bioinform Genomics Proteomics, 2018, 3, 1029.
V.M. Alves, E.N. Muratov, A. Zakharov, N.N. Muratov, C.H. Andrade, T. Tropsha, Food Chem Toxicol, 2018, 112, 526-534.
D. Lagorce, L. Bouslama, J. Becot, M.A. Miteva, B.O. Villoutreix, Bioinformatics, 2017, 33, 3658-3660.
F. Cheng, W. Li, Y. Zhou, J. Shen, Z. Wu, G. Liu, P.W. Lee, Y. Tang, J Chem Inf Model, 2012, 52, 3099-3015.
A. Daina, O. Michielin, V. Zoete, Sci Rep, 2017, 7, Article ID 42717.
R.C. Braga, V.M. Alves, E.N. Muratov, J. Strickland, N. Kleinstreuer, A. Trospsha, C.H. Andrade, Chem Inf Model, 2017, 57, 1013-1017.
V.M. Alves, S.J. Capuzzi, R.C. Braga, J.V.B. Borba, A.C. Silva, T. Luechtefeld, T. Hartung, C.H. Andrade, E.N. Muratov, A. Tropsha, ACS Sustainable Chem Eng, 2018, 6, 2845-2858.
K. Kolsek, J. Mavri, M. Sollner Dolenc, S. Gobec, S. Turk, J Chem Inf Model, 2014, 54, 1254-1264.
W. Gao, C.E. Bohl, J.T. Dalton, Chem Rev, 2005, 105, 3352-3370.
R.C. Braga, V.M. Alves, M.F. Silva, E. Muratov, D. Fourches, L.M. Lião, A. Tropsha, C.H. Andrade, Mol Inform, 2015, 34, 698-701.
G. Patlewicz, N. Jeliazkova, R.J. Safford, A.P. Worth, B. Aleksiev, SAR QSAR Environ Res, 2008, 19, 495-524.
A. Grosdidier, V. Zoete, O. Michielin, Nucleic Acids Res, 2011, 39, W270-W277.
S. Singh, S.S.-L. Li, Genomics, 2011, 97, 148-157.
J.J. Irwin, B.K. Shoichet, J Chem Inf Model, 2005, 45, 177-182.
C.A. Lipinski, F. Lombardo, B. Dominy, P.J. Feeney, Adv Drug Deliv Rev, 1997, 23, 3-25.
W.J. Egan, K.M. Merz, J.J. Baldwin, J Med Chem, 2000, 43, 3867-3877.
D.F. Veber, S.R. Johnson, H.Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple, J Med Chem, 2002, 45, 2615-2623.
M.P. Gleeson, J Med Chem, 2008, 51, 817-834.
J.D. Hughes, J. Blagg, D.A. Price, S. Bailey, G.A. DeCrescenzo, R.V. Devraj, E. Ellsworth, Y.M. Fobian, M.E. Gibbs, R.W. Gilles, N. Greene, E. Huang, T. Krieger-Burke, J. Loesel, T. Wager, L. Whiteley, Y. Zhang, Bioorg Med Chem Lett, 2008, 18, 4872-4875.
Y. Otsubo, T. Nishijo, M. Miyazawa, K. Saito, H. Mizumachi, H. Sakaguchi, Reg Tox Pharm, 2017, 88,118-124.
G.M. Cramer, R.A. Ford, R.L. Hall, Food Cosmet Toxicol, 1978, 16, 255-276.
R. Benigni, C. Bossa, Toxicol Mech Methods, 2008, 18, 137-147.
H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne, Nucleic Acids Res, 2000, 28, 235-242.
E.F. Pettersen, T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng, T.E. Ferrin, J Comput Chem, 2004, 25, 1605-1612.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 Studia Universitatis Babeș-Bolyai Chemia
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
