Registration Dossier

Administrative data

Endpoint:
additional ecotoxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was published in reliable scientific journal. The test course was detailed introduced, so the reliability can be defined as reliable with restrictions.

Data source

Reference
Reference Type:
publication
Title:
Investigation of cytotoxic, genotoxic, mutagenic, and estrogenic effects of the flame retardants tris-(2-chloroethyl)-phosphate (TCEP) and tris-(2-chloropropyl)-phosphate (TCPP) in vitro
Author:
W. Follmann, J. Wober
Year:
2005
Bibliographic source:
Toxicology Letters 161 (2006) 124–134

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
using the recombinant yeast reporter gene assay and by induction of the alkaline phosphatase enzyme in human endometrial cancer Ishikawa cells.
GLP compliance:
not specified
Type of study / information:
Endocrine disrupting effects

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Testing substance was the same with the substance notified in the section 1 of this dossier. tris-(2-chloropropyl)- phosphate (TCPP) (CAS No.: 13674-84-5) was from Akzo-Nobel (Deventer, Netherlands). insulin-transferrin-seleniumA-supplement, DMEM and DMEM/F12 culture medium were from Invitrogen (Eggenstein, Germany), and fetal calf serum from Biochrom (Berlin, Germany). Chlorphenol-red-β-dgalactopyranoside (CRPG) and p-nitrophenylphosphate (NPP) were from Roche (Mannheim, Germany). Sterile plastic materials were from Greiner (Solingen, Germany).

Results and discussion

Any other information on results incl. tables

Induction of the activity of the enzyme alkaline phosphatase in Ishikawa cells (human endometrial adenocarcinoma cell line) is seen as a hint for an estrogenic potential of a test substance. TCPP did not induce activity of alkaline phosphatase in contrast to the positive control (estradiol 1μM).

To confirm the latter results in further screening system estrogen receptor-mediated effects were examined with the Recombinant Yeast Assay with GLAXO ERα yeasts. In this assay an induction ofactivity of β-galactosidase secreted from the GLAXO ERα yeasts demonstrates an estrogenic effect of a test substance. TCPP did not induceβ-galactosidase activity whereas for the positive control (estradiol) clear induction was measured. To test vice versa the antiestrogenic potential of TCPP and TCEP,GLAXO ERα yeasts were induced by estradiol and then treated with the test substances. As demonstrated in, TCPP did not reduce the induction origination from estradiol indicating that both have no antiestrogenic potential.

Applicant's summary and conclusion

Conclusions:
This study was used an advanced method to dig out the oestrogenic or anti-oestrogenic effects of TCPP, so the results were fulfilled all validity criteria.
Executive summary:

Oestrogenic/anti-oestrogenic effects have been investigated by Föllmann and Wober (2006) using the recombinant yeast reporter gene assay and by induction of the alkaline phosphatase enzyme in human endometrial cancer Ishikawa cells. This study was used an advanced method to dig out the oestrogenic or anti-oestrogenic effects of TCPP, so the results were fulfilled all validity criteria. No induction of oestrogenic or anti-oestrogenic effects was detected in either of the test systems.