Registration Dossier

Administrative data

Endpoint:
endocrine system modulation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice
Author:
Kassotis CD, Klemp KC, Vu DC, Chung-Ho L, Meng CX, Besch-Willliford CL, Pinatti L, Zoeller T, Drobnis EZ, Balise VD, Isiguzo CJ, Williams MA, Tillit DE, Nagel SC.
Year:
2015
Bibliographic source:
Endocrinology 156(12), 4458-73
Reference Type:
publication
Title:
Estrogen and Androgen Receptor Activities of Hydraulic Fracturing Chemicals and Surface and Ground Water in a Drilling-Dense Region.
Author:
Kassotis CD, Tillitt DE, Davis JW, Hormann AM, Nagel SC
Year:
2014
Bibliographic source:
Endocrinology, 155(3):897–90

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Measurement of potential for endocrine disrupting activity for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. The hypothesis was that the chemicals used in oil and natural gas operations (including this substance) would exhibit antagonist activities for nuclear hormone receptors.
GLP compliance:
no
Type of method:
in vitro
Endpoint addressed:
toxicity to reproduction / fertility

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Source: Sigma Aldrich. No purity information.

Results and discussion

Any other information on results incl. tables

The results as interpreted from the graphical information presented are as follows:

POSITIVE CONTROL

DEGME

Concentrations in molar

EC10

EC50

EC50/EC10

EC10

EC50

EC50/EC10

Anti-oestrogenic

3x10-11

3x10-10

10

1x10-7

not reached

>1000

Anti-progestogenic

8x10-10

5x10-9

6.3

5x10-5

not reached

>1000

Anti-androgenic

2x10-7

2x10-6

10

4x10-6

not reached

>25

Anti-androgenic*

9x10-8

2x10-6

22

2x10-6

~1x10-4

~50

Anti-glucocorticogenic

2x10-10

7x10-9

35

5x10-5

not reached

Anti-thyroidogenic

1x10-7

1x10-6

10

No effects seen

*HepG-2 liver cancer cell line. All others Ishikawa cell lines

For DEGME, the EC50 was not seen for most end points up to the maximum tested concentration.

Applicant's summary and conclusion

Conclusions:
For a number of reasons, it is difficult to draw conclusions from this study. There are a number of shortcomings, which may be due to deficiencies in the reporting rather than inherent deficiencies in the method, although it is not a validated one, but it means that these results cannot be relied upon as evidence of endocrine effects.
Executive summary:

In an in vitro study using cells transfected with gene reporters, 24 chemicals found in fracking formulations were individually assessed for possible endocrine antagonism effects. DEGME was found to have some activity towards androgen, estrogen, progesterone and thyroid receptors but not thyroid. However, the effects were weak and the dose response curves shallow. IC50 values were not reached for the any of the tests using the Ishikawa cell line up to the maximum tested concentration of 0.1mM and only just seen (IC50 ~0.1mM) for the anti-androgenic activity of the reporter transfected into HepG-2 liver cancer cell line. Overall, the reliability of this study as reported cannot be assessed for a number of reasons, but particularly because no information is provided on the number of replicates or concentrations tested and a complete lack of statistical information.