Hexabromocyclododecane

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not conducted.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

publication

Title:

Modulation at a cellular level of the thyroid hormone receptor mediated gene expression by 1,2,5,6,9,10-hexabromocyclododecane (HBCD), 4,4'-diidophenyl (DIB), and nitrofen (NIP).

Author:

Yamada-Okabe, T., Sakai, H., Kashima, Y. & Yamada-Okabe, H.

Year:

2005

Bibliographic source:

Toxicology Letters (2005), Vol. 155, pp.127-133.

Materials and methods

Type of study / information:

In vitro evaluation of thyroid hormone receptor (TR)-mediated gene expression in HeLaTR cells (stably expressing the humen TRa1) and in MCF7 (which expressed human estrogen receptor a), transfected with a luciferase gene linked to the thyroid responsive element.

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

After transfection with a firely luciferase gene, HeLaTR cells were cultured for 2 days in the presence or absence of 50 ng/ml T3 and the test substance at different concentrations. Similarly, transfected MCF7 cells were coltured for 2 days in the presence or absence of 10-8M estradiol (E2) and the test substance at different concentrations. Thereafter, the cells were harvested, lysed and the luciferase activities in the cell extracts were determined using a luciferase assay kit.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hexabromocyclododecane

EC Number:

247-148-4

EC Name:

Hexabromocyclododecane

Cas Number:

25637-99-4

Molecular formula:

C12H18Br6

IUPAC Name:

(1S,2S,5S,6S,9S,10S)-1,2,5,6,9,10-hexabromocyclododecane

Details on test material:

The 1,2,5,6,9,10-Hexabromocyclododecane (HBCD) was purchased from Tokyo Kasei (Tokyo, Japan).

Results and discussion

Any other information on results incl. tables

In the presence of T3, HBCD at concentrations of 3.12 , 6.25 , and 12.5 µM increased the luciferase activity by about 1.6–1.8-fold that in HeLaTR cells that were exposed to only T3. Whether the effect of HBCD on the luciferase activity was dependent on T3 was also examined. In the absence of T3, exposure of cells up to 25 µM HBCD did not increase in the luciferase activity. Next, whether changes in the luciferase activity by HBCD are the consequence of the stimulation or inhibition of cell growth was investigated. HBCD caused a toxic effect on HeLaTR cells at concentrations higher than 50 µM, but it did not affect the growth of HeLaTR cells at 25 µM or lower concentrations, thus demonstrating that HBCD enhances TR-mediated transcription at concentrations that do not affect the cell growth.

Human TR shares significant sequence similarity with human ERa and ER can associate with TR in vitro. In addition, half of the thyroid

hormone response element (TRE) is identical to the estrogen response element (ERE), and binding of TR to ERE caused the inhibition of estrogen-dependent transactivation. Therefore, whether HBCD enhances ER-mediated gene expression was also investigated. HBCD did not affected the luciferase activity either in the absence or in presence of E2. .

Applicant's summary and conclusion

Conclusions:

HBCD significantly enhanced the expression of the luciferase gene linked to thyroid hormone responsive element at concentrations that did not affected the growth of HeLaTR cells. No activity was detected on the E2-induced expression of the luciferase gene linked to the estrogen responsive element in MCF7 cells.