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

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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.

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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

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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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Authors and Affiliations

  1. CIS Toxicology, Osorno, Chile

    Thomas Colnot

  2. University of Ottawa, Ottawa, Canada

    Sam Kacew

  3. Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078, Würzburg, Germany

    Wolfgang Dekant

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  1. Thomas Colnot
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  2. Sam Kacew
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  3. Wolfgang Dekant
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Correspondence to Wolfgang Dekant.

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Colnot, T., Kacew, S. & Dekant, W. Mammalian toxicology and human exposures to the flame retardant 2,2′,6,6′-tetrabromo-4,4′-isopropylidenediphenol (TBBPA): implications for risk assessment. Arch Toxicol 88, 553–573 (2014). https://doi.org/10.1007/s00204-013-1180-8

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