1,1'-(ethane-1,2-diyl)bis[pentabromobenzene]

Biotransformation and kinetics

Administrative data

Endpoint:

biotransformation and kinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2011-2012

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: See Additional comments

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Comparative hepatic microsomal biotranformation of selectedc PBDEs, including decabromodiphenyl ether, and decabromodiphenyl ethane flame retardants in Arctic marine-feeding mammals.

Author:

McKinney et al.

Year:

2011

Bibliographic source:

Environ Toxicol Chem 2011 30(7):1506-1514

Reference 2

Reference Type:

publication

Title:

Unrecognized causative factors for the lack of in vitro metabolism reported by McKinney et al.

Author:

Hardy M

Year:

2012

Bibliographic source:

Environ Toxicol Chem 31(6):1184-1186.

Reference 3

Reference Type:

publication

Title:

Comparative tissue distribution, biotransformation and associated biological effects by decabromodiphenyl ethane and decabromoinated diphenyl ether in male rats after a 90-day oral exposure study

Author:

Wang et al

Year:

2010

Bibliographic source:

Environ Sci Technol 44:5655-5660

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

in vitro hepatic microsomal systems prepared from several mammalian species. test material incubated with microsomes and disapperance of test material monitored as was metabolites.

GLP compliance:

no

Type of medium:

other: hepatic microsomal preparations from polar bear, beluga whale, ringed seal, and rat

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-(ethane-1,2-diyl)bis[pentabromobenzene]

EC Number:

284-366-9

EC Name:

1,1'-(ethane-1,2-diyl)bis[pentabromobenzene]

Cas Number:

84852-53-9

Molecular formula:

C14H4Br10

IUPAC Name:

1,2,3,4,5-pentabromo-6-[2-(2,3,4,5,6-pentabromophenyl)ethyl]benzene

Test material form:

solid

Results and discussion

Transformation products:

no

Any other information on results incl. tables

Low and variable recovery of EBP. No metabolites identified.

Applicant's summary and conclusion

Conclusions:

DBDP-Ethane did not undergo in vitro metabolism by hepatic microsomes prepared from polar bear, beluga whale, ringed seal and rat liver. "Depletion" of the starting concentration (44 to 74%) was observed, but no metabolites were identified. Non-specific binding to surfaces and particulates and low solubility are likely responsible for the "depletion". Formation of reactive metabolites is unlikey given high NOEL/NOAELs in repeated dose studies.

Executive summary:

McKinney et al. (2011) reported in vitro hepatic microsomal preparations from polar bear, beluga whale, ringed seal, and rat did not metabolize decabromodiphenyl ethane, BDE 209, 99, 100 or 154. As commented by Hardy (2012), the low and variable recoveries of BDE 209 (81 +/- 9%) and DBDP-Ethane (49 +/- 23%) in the controls, and the "depletion" observed in the test groups, 14 to 25% for BDE 209 and 44 to 74% for DBDP-Ethane, in the absence of identified metabolites suggest that factors other metabolic conversion may be responsible. Hardy (2012) noted that both substances are highly insoluble in aqueous media and many organic solvents, and are prone to non-specific binding to surfaces and particulates. Low solubility compounds are not properly assayed by many in vitro systems due to their precipitation and/or adherence to walls of the vessel, which eliminates interaction with microsomal enzymes (Kerns and Di 2008). In GLP/guideline mutagenicity tests and bi-directional cell permeability assays, poor solubility was observed with DBDPEthane and BDE 209 (see Griffen 2008, Section 7). The ability to detect BDE 209 and DBDPEthane in the cell permiability assays was similar to McKinney et al.'s pattern of recovery (higher for BDE 209 than DBDP-Ethane). (See Hardy 2012 for details.) McKinney et al. commented that the low recovery of DBDPEthane may be due to binding of reactive metabolites. However, NOELs/NOAELs of >= 1000 mg/kg/d in repeated dose studies indicate that significant amounts of reactive metabolites are not formed from DBDPEthane. He et al. reported that lower brominated diphenyl ethanes were not detected in rat tissues after 90-d oral administration of 100 mg/kg/d.