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 DekantEmail author
Review Article


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.


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

Lists of abbreviations


Absorption, distribution, metabolism, and excretion


Androgen receptor


Benchmark dose


Body weight


N-nitroso bis(2-hydroxypropyl)amine






European chemicals agency


Estrogen receptor


European Union


Gestational day


Good laboratory practice




Limits of detection








Organisation for economic co-operation and development




Peroxisome proliferator–activated receptors


Progesterone receptor






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


Thyroid hormone


Thyroid hormone-binding transport protein



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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