title: Development of toxicity values and exposure estimates for tetrabromobisphenol A: application in a margin of exposure assessment.
abstract: Tetrabromobisphenol A (TBBPA) is used in a diverse array of products to improve fire safety. The National Toxicology Program (NTP) recently completed a 2-year bioassay for TBBPA. The objective of the present study was to develop a cancer-based and a non-cancer based toxicity value and to compare such to appropriate estimates of human exposure. Data from the NTP 2-year and 13-week studies were selected to develop candidate toxicity values. Benchmark dose modeling and subsequent evaluation of candidate values resulted in selection of an oral reference dose (RfD) of 0.6 mg kg(-1) day(-1) based on uterine hyperplasia in rats and an oral cancer slope factor (OSF) of 0.00315 per mg kg(-1) day(-1) based on an increased incidence of uterine tumors in rats. Lifetime average daily dose (LADD) estimates ranged from 2.2 E(-7) to 3.9 E(-6) mg kg(-1) day(-1) based on age-adjusted exposures to TBBPA via breast milk consumption, dietary intake, soil/dust ingestion and drinking water ingestion in infants, young children, older children and adults. Average daily dose (ADD) estimates ranged from 3.2 E (-7) to 8.4 E(-5) mg kg(-1) day(-1). Resulting margin of exposure (MOE) values were > 800 000 for non-cancer endpoints and > 32,000,000 for cancer-based endpoints. These data collectively indicate a low level of health concern associated with exposures to TBBPA based on current data. It is anticipated that the exposure estimates, along with the toxicity values described within, should be informative for understanding human health hazards associated with TBBPA.
authors.affiliation: ToxStrategies Inc., Austin, TX, 78759, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Wikoff
authors.affiliation: ToxStrategies Inc., Houston, TX, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Thompson
authors.affiliation: ToxStrategies Inc., Austin, TX, 78759, USA.
authors.forename: Camarie
authors.initials: C
authors.lastname: Perry
authors.affiliation: ToxStrategies Inc., Austin, TX, 78759, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: White
authors.affiliation: ToxStrategies Inc., Cary, NC, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Borghoff
authors.affiliation: ToxStrategies Inc., Austin, TX, 78759, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Fitzgerald
authors.affiliation: ToxStrategies Inc., Austin, TX, 78759, USA.
authors.forename: Laurie C
authors.initials: LC
authors.lastname: Haws
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water / Q000032:analysis; D004391:Dust / Q000032:analysis; D023381:Endpoint Determination; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007223:Infant; D008297:Male; D051379:Mice; D008895:Milk, Human / Q000737:chemistry; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051381:Rats; D018675:Toxicity Tests; D014594:Uterine Neoplasms / Q000139:chemically induced / Q000473:pathology
chemical_list: D060766:Drinking Water; D004391:Dust; D011075:Polybrominated Biphenyls; C020806:tetrabromobisphenol A
keywords: RfD; TBBPA; cancer slope factor; flame retardant; margin of exposure; toxicity value
references.citation: Am J Pathol. 1953 Sep-Oct;29(5):853-9
references.pmid: 13092222
references.citation: Environ Pollut. 2013 Aug;179:105-10
references.pmid: 23665846
references.citation: Arch Toxicol. 2014 Mar;88(3):553-73
references.pmid: 24352537
references.citation: Toxicol Lett. 2009 Mar 28;185(3):160-7
references.pmid: 19152830
references.citation: Environ Sci Technol. 2010 Jun 1;44(11):4198-202
references.pmid: 20441148
references.citation: Reprod Toxicol. 2009 Dec;28(4):456-67
references.pmid: 19577631
references.citation: Environ Sci Technol. 2009 Jun 15;43(12):4314-9
references.pmid: 19603640
references.citation: Mol Cell Endocrinol. 2010 Jul 29;323(2):172-82
references.pmid: 20399831
references.citation: Environ Int. 2003 Sep;29(6):829-39
references.pmid: 12850099
references.citation: Science. 1980 Aug 29;209(4460):1023-6
references.pmid: 7403864
references.citation: Chemosphere. 2002 Feb;46(5):583-624
references.pmid: 11999784
references.citation: J Appl Toxicol. 2015 Nov;35(11):1292-308
references.pmid: 25825072
references.citation: Reprod Toxicol. 2013 Jan;35:32-9
references.pmid: 22677475
references.citation: EFSA J. 2024 Jul 15;22(7):e8859
references.pmid: 39010865
references.citation: Environ Sci Technol. 2008 Sep 15;42(18):6855-61
references.pmid: 18853800
references.citation: Toxicol Sci. 2005 Apr;84(2):249-59
references.pmid: 15635150
references.citation: J Toxicol Environ Health A. 2009;72(21-22):1439-45
references.pmid: 20077216
references.citation: Toxicology. 2006 Feb 1;218(2-3):229-36
references.pmid: 16325980
references.citation: Environ Sci Technol. 2009 Dec 15;43(24):9077-83
references.pmid: 19921842
references.citation: Regul Toxicol Pharmacol. 2007 Jul;48(2):184-93
references.pmid: 17507125
references.citation: Arch Toxicol. 2012 Sep;86(9):1431-42
references.pmid: 22415764
references.citation: Toxicol Rep. 2014;1:214-223
references.pmid: 24977115
references.citation: Environ Pollut. 2014 Jan;184:193-200
references.pmid: 24060738
references.citation: Int Immunopharmacol. 2010 Apr;10(4):393-7
references.pmid: 20074668
references.citation: Toxicol Sci. 2006 Jul;92(1):157-73
references.pmid: 16601080
references.citation: Toxicol Lett. 2004 Apr 21;150(2):145-55
references.pmid: 15093670
references.citation: Toxicology. 2000 Jan 3;142(2):87-95
references.pmid: 10685508
references.citation: Toxicol Pathol. 2002 Sep-Oct;30(5):580-91
references.pmid: 12371667
references.citation: Chemosphere. 2002 Feb;46(5):709-16
references.pmid: 11999794
references.citation: J Toxicol Environ Health B Crit Rev. 2010;13(5):411-48
references.pmid: 20582854
references.citation: Sci Total Environ. 2013 May 1;452-453:10-8
references.pmid: 23500394
references.citation: Food Chem Toxicol. 2010 Jan;48 Suppl 1:S2-24
references.pmid: 20113851
references.citation: Anal Bioanal Chem. 2010 Jan;396(2):865-75
references.pmid: 19921511
references.citation: Toxicology. 2008 Apr 3;246(1):45-54
references.pmid: 18295390
references.citation: Toxicol Appl Pharmacol. 2004 Dec 15;201(3):226-94
references.pmid: 15582646
references.citation: Sci Total Environ. 2013 Aug 1;458-460:15-9
references.pmid: 23639907
references.citation: Toxicol In Vitro. 2010 Feb;24(1):201-7
references.pmid: 19765641
references.citation: Chemosphere. 2008 Oct;73(7):1036-41
references.pmid: 18790516
references.citation: Environ Toxicol Pharmacol. 2007 Mar;23(2):174-8
references.pmid: 21783755
references.citation: Environ Sci Pollut Res Int. 2012 Nov;19(9):4090-6
references.pmid: 22825637
references.citation: Regul Toxicol Pharmacol. 1997 Feb;25(1):1-5
references.pmid: 9056496
references.citation: Environ Health Perspect. 2004 Jan;112(1):9-17
references.pmid: 14698924
references.citation: Environ Health Perspect. 2013 Oct;121(10):1194-9
references.pmid: 23959441
references.citation: Food Chem Toxicol. 2006 Aug;44(8):1408-13
references.pmid: 16716481
references.citation: Toxicology. 2008 Mar 12;245(1-2):76-89
references.pmid: 18255212
references.citation: Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008 Jul;25(7):895-903
references.pmid: 18569008
references.citation: Environ Health Perspect. 2014 May;122(5):499-505
references.pmid: 24569956