1,2-Ethandiylbis(oxy-2,1-ethandiyl)-dimethansulfonat

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo, other

Remarks:

Combined in vivo comet assay and micronucleus test for detection of test item potential to induce chromosomal aberrations or gene mutations in vivo

Type of information:

experimental study planned

Study period:

2023-2024 // The study will be conducted after a decision on the requirement to carry out the proposed test has been taken according to the procedure laid down in Regulation (EC) 1907/2006, and a deadline to submit the information required has been set

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS
A testing proposal for an in vivo combined comet assay and micronucleus test according to the OECD guidelines 489 and 474, respectively, has been submitted by the registrant in order to meet the information required of Section 8.4 of Annex VII and VIII of the REACH Regulation.
An Ames test in accordance with OECD Guideline 471 was performed using Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli strain WP2 uvrA with and with metabolic activation. The study showed positive results in Salmonella typhimurium strains TA100 and TA1535 with and without metabolic activation. Therefore, the Ames test was concluded to be positive. Furthermore, an in vitro mammalian cell micronucleus test was performed in accordance with OECD Guideline 487. The test item induced biologically and statistically significant increases breakage and /or chromosomal loss in L5178Y cells after 4- and 24-hours treatment both in the absence and in the presence of metabolic activation when compared to the negative and the historical controls, and was therefore considered as genotoxic in the in vitro micronucleus test.
Due to the positive in vitro study results, further in vivo testing is deemed required in accordance with column 2 of Annex VIII of the REACH Regulation. In line with the ECHA recommendation on standard information requirements for Mutagenicity for substances which raise concerns for both gene mutation and chromosomal aberration, the registrant considers the testing proposal for a combined in vivo comet assay (OECD Test Guideline 489) and an in vivo micronucleus test (OECD TG 474) as justified.


NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: 2-[2-(2-hydroxyethoxy)ethoxy]ethanol,methanesulfonic acid


CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies: no GLP studies available to cover this endpoint
- Available non-GLP studies: no non-GLP studies available to cover this endpoint
- Historical human/control data: no historical human data available to cover this endpoint
- (Q)SAR: (Q)SAR methods are not expected to generate data which prevent the need for in vivo testing of the substance
- In vitro methods: both in vitro tests gave positive results, therefore further in vivo testing is required
- Weight of evidence: no appropriate weight of evidence information is available to cover this endpoint
- Grouping and read-across: read-across was considered; however it has been concluded that no appropriate information from related or appropriate source substances is available to cover this endpoint
- Substance-tailored exposure driven testing [if applicable]: not applicable
- Approaches in addition to above [if applicable]: not applicable
- Other reasons [if applicable]: not applicable

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- There are no adequate specific adaptation possibilities that allow generation of the necessary information.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed: the proposed testing will be run according to OECD Guidelines 489 (in vivo mammalian alkaline comet assay) and OECD Guideline 474 (mammalian erythrocyte micronucleus test).

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

29 Jul 2016

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)

Version / remarks:

29 Jul 2016

GLP compliance:

yes (incl. QA statement)

Type of assay:

other: combined in vivo comet assay (OECD Test Guideline 489) and an in vivo micronucleus test (OECD TG 474)

Test material

Test material information

Constituent 1

Reference substance name:

2-[2-(2-hydroxyethoxy)ethoxy]ethanol,methanesulfonic acid

Cas Number:

80322-82-3

Molecular formula:

C8H18O8S2

IUPAC Name:

2-[2-(2-hydroxyethoxy)ethoxy]ethanol,methanesulfonic acid

impurity 1

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Oxidane

impurity 2

Reference substance name:

1,2-Ethandiylbis(oxy-2,1-ethandiyl)-monomethanesulfonat

IUPAC Name:

1,2-Ethandiylbis(oxy-2,1-ethandiyl)-monomethanesulfonat

Test material form:

liquid

Details on test material:

Appearance: Dark yellow liquid
Batch No.: 01110008
Storage: -5 – 40 °C, container tightly closed, protected from light

Test animals

Species:

rat

Administration / exposure

Route of administration:

oral: gavage