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Archives of Toxicology

, Volume 88, Issue 3, pp 553–573 | Cite as

Mammalian toxicology and human exposures to the flame retardant 2,2′,6,6′-tetrabromo-4,4′-isopropylidenediphenol (TBBPA): implications for risk assessment

  • Thomas Colnot
  • Sam Kacew
  • Wolfgang Dekant
Review Article

Abstract

The compound 2,2′,6,6′-Tetrabromo-4,4′-isopropylidenediphenol (tetrabromobisphenol A, TBBPA) is used as a reactive and additive flame retardant. This review evaluates the mammalian toxicology of TBBPA and summarizes recent human exposure and risk assessments. TBBPA has a low potential for systemic or reproductive toxicity, and no-observed-adverse-effect-levels were greater than 1,000 mg/kg body weight (bw)/day in a 90-day oral toxicity study, a developmental toxicity study and a two-generation reproductive and developmental toxicity study. Some interactions of TBBPA with hormone-mediated pathways were noted in vitro; however, when studied in vivo, TBBPA did not produce adverse effects that might be considered to be related to disturbances in the endocrine system. Therefore, in accordance with internationally accepted definitions, TBBPA should not be considered an “endocrine disruptor.” Furthermore, TBBPA is rapidly excreted in mammals and therefore does not have a potential for bioaccumulation. Measured concentrations of TBBPA in house dust, human diet and human serum samples are very low. Daily intakes of TBBPA in humans were estimated to not exceed a few ng/kg bw/day. Due to the low exposures and the low potential for toxicity, margins of exposures for TBBPA in the human population were between 6 × 104 (infants) to 6 × 107 (adults). Exposures of the general population are also well below the derived-no-effect-levels derived for endpoints of potential concern in REACH.

Keywords

Endocrine toxicity Exposure assessment Repeated-dose toxicity Role of in vitro assays Two-generation studies Toxicokinetics Bioaccumulation 

Lists of abbreviations

ADME

Absorption, distribution, metabolism, and excretion

AR

Androgen receptor

BMD

Benchmark dose

Bw

Body weight

DHPN

N-nitroso bis(2-hydroxypropyl)amine

DMBA

7,12-Dimethylbenz(a)anthracene

DNEL

Derived-no-effect-level

ECHA

European chemicals agency

ER

Estrogen receptor

EU

European Union

GD

Gestational day

GLP

Good laboratory practice

LOAEL

Lowest-observed-adverse-effect-level

LOD

Limits of detection

MoE

Margin-of-exposure

MOS

Margin-of-safety

NOAEL

No-observed-adverse-effect-level

OECD

Organisation for economic co-operation and development

PoD

Point-of-departure

PPAR

Peroxisome proliferator–activated receptors

PR

Progesterone receptor

T3

Triiodothyronine

T4

Thyroxine

TBBPA

2,2′,6,6′-Tetrabromo-4,4′-isopropylidenediphenol; tetrabromobisphenol A

TH

Thyroid hormone

TTR

Thyroid hormone-binding transport protein

Notes

Acknowledgments

The preparation of this review was supported in part through an honorarium to Thomas Colnot and Sam Kacew from the Bromine Science and Environmental Forum (BSEF), which is the bromine industry’s global organization. Work in Wolfgang Dekants laboratory on TBBPA was supported by the fifth Framework Programme of the European Commission in the “FIRE” project. This review represents the individual professional views of the authors.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.CIS ToxicologyOsornoChile
  2. 2.University of OttawaOttawaCanada
  3. 3.Department of ToxicologyUniversity of WürzburgWürzburgGermany

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