Registration Dossier

Administrative data

Description of key information

The derived irritation/corrosion effects from the key studies were:
Neither irritating nor corrosive effects observed, according to OECD 404, Clariant, 1995;

No eye irritating effect observed, according to OECD 405, Clariant, 1995.

B-TEGME applied as pure substance and in brake fluids (testing mixtures) was very well tolerated in rats after both dermal and ocular testing for irritation and corrosion. Scoring values were consistent between studies, therefore the studies were considered to be adequate and  reliable and  the test substance is considered to be safe. B-TEGME has no irritating or corrosion potential.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-03-07 to 1995-03-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
17 July 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: Partie 24, 05-Jan-1995; Product number / code: LP 1941
- Substance type: Borated Glycol Ether
- Expiration date of the lot/batch: stable until 05-Jul-1995
- Purity test date: Not provided
- Analytical purity: 97% (calculated after titration of boric acid)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Chemical pharmaceutical factory Dr. K. Thomae, 88400 Biberach, Germany; SPF breed
- Age at study initiation: 3-5 months
- Weight at study initiation: 2.8-3.2 kg
- Housing: separate cages (arranged in a battery), air-conditioned rooms
- Diet: ssniff K-H (V2333) ad libitum and hay (approx. 15 g daily)
- Water: from automatic dispensers ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1995-03-07 To 1995-03-10
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml per patch (undiluted)
- Concentration (if solution): 100% (undiluted)
VEHICLE: not applicable
Duration of treatment / exposure:
4 hours
Observation period:
Examinations of the skin took place after 30-60 minutes as well as 24, 48 and 72 hours after removal of the patches.
Number of animals:
3
Details on study design:
TEST SITE
- The dorsal region of the body was removed by an electric clipper over an area of 25 cm2.
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100% cellulose patch on a piece of surgical plaster
- Type of wrap used: semi-occlusive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): all remnants of the test substance were carefully removed from the skin with warm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD 404
Erythema and Eschar Formation
- No erythema ...0
- Very slight erythema (barely perceptible) ...1
- Well defined erythema ...2
- Moderate to severe erythema ...3
- Severe erythema (beef redness) to eschar formation preventing grading of erythema...4
- Not assessable ...*
- Maximum possible: 4

Oedema Formation
- No oedema...0
- Very slight oedema (barely perceptible) ...1
- Slight oedema (edges of area well defined by definite raising) ...2
- Moderate oedema (raised approximately 1 mm) ...3
- Severe oedema (raised more than 1 mm and extending beyond area of exposure) ...4
- Not assessable ...*
- Maximum possible: 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No signs of irritation were observed during the study.
For further details, see table 1.

Table 1. Dermal irritation testing in rabbits

Animal No.

Erythema

Mean score

Oedema

Mean score

30-60 minutes

1 day

2 days

3 days

30-60 minutes

1 day

2 days

3 days

159

0

0

0

0

0.0

0

0

0

0

0.0

160

0

0

0

0

0.0

0

0

0

0

0.0

161

0

0

0

0

0.0

0

0

0

0

0.0

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the results of the study B-TEGME is not irritating to the skin.
Executive summary:

In an acute dermal irritation/corrosion study according to OECD 404, three New Zealand White rabbits were dermally exposed with the test substance.

Semi-occlusive testing of 0.5 ml undiluted B-TEGME for 4 hours showed neither erythma nor oedema on any of the three rabbits after the exposure and observation time points.

It can be occluded that B-TEGME is not irritating to the skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-03-21 to 1995-03-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
31 July 1992
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Substance type: Borated Glycol Ether
- Physical state: Clear colourless liquid
- Analytical purity: 97% (calculated after titration of boric acid)
- Purity test date: Not provided
- Lot/batch No.: Partie 24, 05-Jan-1995 (stable until 05-Jul-1995); code No. LP 1941
- Expiration date of the lot/batch: 1995-07-05
- Stability under test conditions: 1995-07-05
Species:
rabbit
Strain:
New Zealand White
Remarks:
Chbb: NZW (SPF)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Chemical pharmaceutical factory Dr. K. Thomae, 88400 Biberach, Germany; SPF breed
- Age at study initiation: 3-5 monhts
- Weight at study initiation: 3.4-3.8 kg
- Housing: separate caging, arranged in battery
- Diet: ssniff K-H (V2333) ad libitum and hay (approximately 15 g daily)
- Water: from automatic dispensers ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): No data (airconditioned)
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1995-03-21 to 1995-03-31
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml applied to the conjuctival sac of the left eye
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours after application
At 24 and 72 hours, the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01% fluorescein-sodium solution.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: The treated eyes were washed out thorougly with isotonic saline approx. 37°C at 24h after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution took place.
- Time after start of exposure: directly

SCORING
Ocular reactions:
In addition, discharge was scored as follows:
0: No discharge
1: Any amount different from normal (does not include small amounts normally observed in inner canthus)
2: Discharge with moistening of the lids and hairs just adjacent to the lids
3: Discharge with moistening of the lids and hairs and considerable area around the eye
The mean scores at each time point and the group mean scores at 24, 48 and 72 hours were calculated.
TOOL USED TO ASSESS SCORE: 1 drop of 0.01% fluorescein sodium solution under UV at 24 and 72 hours after application.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
One hour to 2 days after application the conjuctivae of the animals were hyperaemic to a diffuse, crimson color. Obvious swelling was observed one hour after application in one animal. Additionally, clear colorless discharge was observed. Three days after application all irritations were reversible. There were no ocular lesions observed by UV examination.
For further details, please refer to the tables 1 and 2.

Table(s) 1: Eye irritation testing in rabbits with results of all parameters

Animal No.

Cornea opacity

Mean score

Iris changes

Mean score

1 hour

1 day

2 days

3 days

1 hour

1 day

2 days

3 days

116

0

0

0

0

0.0

0

0

0

0

0.0

186

0

0

0

0

0.0

0

0

0

0

0.0

188

0

0

0

0

0.0

0

0

0

0

0.0

 

Animal No.

Conjunctivae redness

Mean score

Chemosis of conjunctivae

Mean score

1 hour

1 day

2 days

3 days

1 hour

1 day

2 days

3 days

116

1

1

0

0

0.3

0

0

0

0

0.0

186

2

2

1

0

1.0

2

0

0

0

0.0

188

1

1

1

0

0.7

0

0

0

0

0.0

 

Animal No.

Conjunctivae discharge

1 hour

1 day

2 days

3 days

116

1

0

0

0

186

1

0

0

0

188

2

0

0

0

Table 2: Mean scores of the performed observation paramters

Group mean 24, 48 & 72 hours

Redness

0.7

Chemosis

0.0

Opacity

0.0

Iris

0.0

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the results of the study B-TEGME is not irritating to eyes.
Executive summary:

In an acute eye irritation/corrosion study according to OECD 405, three New Zealand White rabbits were exposed with the test substance.

Testing of 0.1 ml applied to the left eye of undiluted B-TEGME for 24 hours and subsequent washing with isotonic saline showed redness and discharge observed initially, however this disappeared within 3 days after dosing.

The substance was not irritating to the eyes after the exposure and the relevant observation time points.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for dermal irritation was conducted in vivo by semi-occlusive testing of undiluted B-TEGME on rabbit skin at the dose of 0.5 ml during 4 hours, demonstrating that the substance was not irritating to the skin up to 7 days after application (Clariant, 95.0104, 1995). This study was applied according to OECD 404 guideline/EU method B.4 and in compliance with GLP, therefore it was considered to be adequate, reliable and relevant.
In addition, there were supporting studies with B-TEGME containing brake fluids. Two brake fluids, one containing 17% B-TEGME (
Shell, SBGR.92.011, 1992) and one containing 37% B-TEGME (Shell, SBGR.90.189, 1990) were also tested by semi-occlusive topical application on rabbit skin for 4 hours. These studies were considered to be supportive because they contained other constituents that may have unknown properties. No irritation/corrosion potential or other dermal changes however were observed up to 7 days after administration. In a third supportive study, B-TEGME applied to rabbit skin (for 1, 5, 15 and 20h) and rabbit ear (for 20h) induced doubtful erythema only after 20h exposure to the skin and ear (BASF, XXIII 535, 1974). Observations on day 8 after exposure did not reveal any findings. The study did not provide many details on test material and test conditions, therefore the results were considered less reliable.

The key study for eye irritation was conducted in vivo on rabbit eyes by testing B-TEGME at the dose of 0.1 ml, demonstrating that the substance was not eye irritating (Clariant, 95.0104, 1995). This study was performed according to OECD 405 guideline and in compliance with GLP, therefore it was considered to be adequate, reliable and relevant.

In addition, there were supporting studies with B-TEGME containing brake fluids, one containing 17% B-TEGME (Shell, SBGR.92.011, 1992) and one containing 37% B-TEGME (Shell, SBGR.90.189, 1990). These studies were considered to be supportive because the other constituents of the brake fluids may have unknown properties. Some conjunctival irritation was observed, however resolving within 48-72 hours of treatment. Other components in the brake Fluid may have contributed to these slight findings. The cornea and iris were not visibly affected by the test material. In a third supportive study, B-TEGME was applied undiluted to rabbit eyes and elicited slight but reversible irritation effects at 1 and 24 hours, but not at 8 days (BASF, XXIII 535, 1974). For this study, there were almost no details on test material and test conditions, therefore the study is not very reliable.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.