Registration Dossier

Administrative data

Endpoint:
monitoring data
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose:
reference to same study
Reference
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
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
Specific details on test material used for the study:
Source: Sigma Aldrich. No purity information.

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.

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.

Data source

Reference
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

Materials and methods

Test guideline
Qualifier:
no guideline required
Type of measurement:
concentration at contaminated site
Media:
other: waste water

Test material

Reference
Name:
Unnamed
Type:
Constituent

Study design

Details on sampling:
- Geographic coordinates:
- Known emission sources near sampling site: Three oil and gas wastewater samples from fracking operations were collected in Garfield County, Colorado, USA either directly from the source or from immediate spills of these fluids into the environment.
- Period of sampling: no data
- Sampling: Sample 1 was collected from a ruptured waste water pipeline that was actively leaking. This sample separated into organic and aqueous layers after collection, and these phases were analyzed separately. Samples 2 and 3 were collected from recovered fluids stored in collection tanks. Sample 1 was collected from an open WW storage tank, and sample 2 was collected from a closed WW storage tank.
- Sample storage before analysis: samples were shipped in glass containers on ice to and stored at 4°C until processing. Aliquots for analytical investigation were stored in volatile organic chemical (VOC)-certified vials at 20°C.

Results and discussion

Concentration
Remarks on result:
other: substance below LOD in all samples tested

Any other information on results incl. tables

The LOD for this substance for the method used seems quite high which rather minimises the value of the information provided.

Applicant's summary and conclusion