title: Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic model.
abstract: Human bioaccumulative potential is an important element in the risk assessment of chemicals. Due to the high number of synthetic chemicals, there exists the need to develop prioritisation strategies. The purpose of this study was to develop a predictive tool for human bioaccumulation risk assessment that incorporates not only the chemical properties of the compounds, but also the processes that tend to decrease the concentration of the compound such as metabolisation. We used a generic physiologically based toxicokinetic model that based on in vitro human liver metabolism data, minimal renal excretion and a constant exposure was able to assess the bioaccumulative potential of a chemical. The approach has been analysed using literature data on well-known bioaccumulative compounds and liver metabolism data from the ECVAM database and a subset of the ToxCast phase I chemical library-in total 94 compounds covering pharmaceuticals, plant protection products and industrial chemicals. Our results provide further evidence that partitioning properties do not allow for a reliable screening criteria for human chemical hazard. Our model, based on a 100% intestinal absorption assumption, suggests that metabolic clearance, plasma protein-binding properties and renal excretion are the main factors in determining whether bioaccumulation will occur and its amount. It is essential that in vitro metabolic clearance tests with metabolic competent cell lines as well as plasma protein-binding assays be performed for suspected bioaccumulative compounds.
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Ispra, VA, Italy.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Tonnelier
authors.forename: Sandra
authors.initials: S
authors.lastname: Coecke
authors.forename: José-Manuel
authors.initials: JM
authors.lastname: Zaldívar
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D010599:Pharmacokinetics; D011485:Protein Binding; D018570:Risk Assessment
chemical_list: D001798:Blood Proteins
references.citation: Environ Toxicol Chem. 2008 Feb;27(2):341-51
references.pmid: 18348640
references.citation: Regul Toxicol Pharmacol. 2011 Feb;59(1):157-75
references.pmid: 21168463
references.citation: SAR QSAR Environ Res. 2005 Dec;16(6):531-54
references.pmid: 16428130
references.citation: Environ Sci Technol. 2004 Apr 15;38(8):2406-12
references.pmid: 15116847
references.citation: Environ Sci Technol. 1982 May 1;16(5):274-8
references.pmid: 22257252
references.citation: Toxicol Sci. 2010 Oct;117(2):348-58
references.pmid: 20639261
references.citation: Sci Total Environ. 2011 Apr 1;409(9):1726-31
references.pmid: 21334727
references.citation: Chemosphere. 2006 Aug;64(9):1582-91
references.pmid: 16403420
references.citation: Toxicol Appl Pharmacol. 1998 Jul;151(1):110-6
references.pmid: 9705893
references.citation: Environ Sci Technol. 2006 Dec 1;40(23):7157-66
references.pmid: 17180962
references.citation: Psychiatry Res. 1988 Jan;23(1):1-10
references.pmid: 3363012
references.citation: J Vet Pharmacol Ther. 1996 Aug;19(4):305-11
references.pmid: 8866460
references.citation: Expert Opin Drug Metab Toxicol. 2009 Feb;5(2):211-23
references.pmid: 19199378
references.citation: Environ Sci Technol. 2011 Jan 1;45(1):197-202
references.pmid: 20701275
references.citation: Environ Toxicol Chem. 2004 Oct;23(10):2356-66
references.pmid: 15511098
references.citation: Chemosphere. 2009 Feb;74(8):1044-52
references.pmid: 19068265
references.citation: Environ Sci Technol. 2006 Jan 1;40(1):53-60
references.pmid: 16433332
references.citation: Front Pharmacol. 2010 Aug 06;1:10
references.pmid: 21607061
references.citation: ALTEX. 2009;26(3):214-22
references.pmid: 19907907
references.citation: Environ Sci Technol. 2001 Jan 15;35(2):325-34
references.pmid: 11347605
references.citation: J Pharm Sci. 2008 Oct;97(10):4586-95
references.pmid: 18300299
references.citation: Environ Toxicol Pharmacol. 2003 Feb;13(2):57-149
references.pmid: 21782649
references.citation: Chemosphere. 2011 Feb;82(9):1268-76
references.pmid: 21196025
references.citation: Eur J Pharm Sci. 2010 Mar 18;39(5):298-309
references.pmid: 20025966
references.citation: Int J Environ Res Public Health. 2011 Feb;8(2):435-55
references.pmid: 21556195
references.citation: Rev Environ Contam Toxicol. 2003;176:1-66
references.pmid: 12442503
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Oct 20;843(1):47-56
references.pmid: 16815762
references.citation: Arch Toxicol. 2011 May;85(5):367-485
references.pmid: 21533817
references.citation: J Pharm Sci. 2004 Apr;93(4):847-54
references.pmid: 14999723
references.citation: Ecotoxicol Environ Saf. 2011 Mar;74(3):244-52
references.pmid: 21040971
references.citation: Toxicol Appl Pharmacol. 1981 Sep 30;60(3):509-26
references.pmid: 7292490