Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial Reverse Mutation data

Protocol
[Klimisch rating]

Strains tested

Positive and negative controls

Maximum tested dose

Result with and without metabolic activation

Reference

Data for DEGME

OECD 471
[2]

TA 98, 100, 1535, 1537,

Yes

5mg/plate

Without: Negative
With: Negative

BASF AG (1989)

Data for DEGEE

OECD 471
[1]

TA 98, 100, 102, 1535, 1537

Yes

5mg/plate

Without: Negative
With: Negative (S9)

Aujoulat (1999)

Data for DEGBE

Equivalent or similar to OECD 471
[2]

TA 98, 100, 1535, 1537, 1538

Yes

20mg/plate

Without: Negative
With: Negative (S9)

Thompson (1984)

Data for TEGME

Equivalent or similar to OECD 471
[1]

TA 98, 100, 1535, 1537, 1538, E coliWP2 uvrA

Yes

10mg/plate first experiment, 5mg/plate second experiment

Without: Negative
With: Negative (rat S9)

Muller (1988)

Data for EGnPE

OECD 471
[1]

TA 98, 100, 1535, 1537, E coliWP2 uvrA

Yes

5mg/plate

Without: Negative
With: Negative

Harlan Laboratories Ltd (2011a)

There are a further three negative studies available on TEGME and one further negative study on DEGBE and DEGME. None of these studies were used as key studies for their respective substances and are therefore not reported further here. All are completely consistent with the results presented in the table above.

Cytotoxicity data    

 

Protocol
[Klimisch rating]

Species/strain

Positive and negative controls

Maximum tested dose

Result with and without metabolic activation

Reference

Data for EGnPE

OECD 473 (CA)
[1]

Human Lymphocytes

Yes

1mg/mL

Without: Negative
With: Negative

Harlan Laboratories Ltd (2011b)

Data for DEGBE

Equivalent or similar to OECD 473 (CA)
[2]

CHO

Yes

5mg/mL

Without: Negative
With: Negative (rat S9)

Thompson (1984)

Data for TEGME

OECD 473 (CA)*
[1]

CHO

Yes

5mg/mL

Without: Negative
With: Negative (rat S9)

Brooks (1992)

*test material a formulated brake fluid comprising 30-40% of TEGME

Mammalian cell gene mutation data

 

Protocol
[Klimisch rating]

Strains tested-Target gene

Positive and negative controls

Maximum tested dose

Result with and without metabolic activation

Reference

Data for EGnPE

OECD 476
[1]

ML-L5178Y

Yes

1mg/mL

Without: Negative
With: Negative

Harlan Laboratories Ltd (2011c)

Data for DEGBE

Equivalent or similar to OECD 476
[1]

CHO-HPGRT

Yes

5mg/mL

Without: Negative
With: Negative (rat S9)

Dow (1987), Gollapudi (1993)

Data for TEGME

EPA OTS 798.5300
[1]

CHO-HPGRT

Yes

5mg/mL

Without: Negative
With: Negative (rat S9)

Dow (1990a)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Protocol
[Klimisch rating]

Species and strain used

Positive and negative controls

Maximum tested dose and exposure period

Result

Reference

Data for DEGEE

Equivalent or similar to OECD 474 (micronucleus)
[2]

Mouse
CD1 (male)

Yes

2mL/day for 3 days ip. Single limit dose used.

Negative

Berte (1986)

Equivalent or similar to OECD 486 (UDS)
[1]

Rat
Wistar (male)

Yes

2000mg/kg single limit dose po.

Negative

Clare (1996)

Data for DEGBE

Equivalent or similar to OECD 475 (CA)
[2]

Mouse
CD1 (male/female)

Yes

3300mg/kg single MTD dose po.

Negative

Gollapudi (1993)

Data for TEGME

EPA OTS 798.5395 (MN)
[1]

Mouse
CD1 (male/female)

Yes

2000mg/kg single dose po.

Negative

Dow (1990b)

There is a negative drosophilia study using DEGBE. This was not used as key studies for DEGBE and therefore not reported further here.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

The in vitro information covering the three required study end points for REACH of bacterial reverse mutation, cytogenicity in mammalian cells and mammalian cell gene mutation is consistently negative for all of the source substances. In the limited cases where there is any possible interpretation of equivocal results, in vivo data is available to provide re-assurance that all of the source substances are negative for mutagenic potential. The shared structural elements and common metabolic pathways across the source and target substances provides confidence in the reliability of using read across data for fulfilling the requirements for this end point for TEGEE and the data leads to the conclusion there is no evidence that TEGEE will have any mutagenic potential. Classification for this end point is not required.