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Administrative data

Description of key information

Skin irritation

Two key GLP OECD 404 studies are available for the assessment of skin irritation (Hoff 1999, Thouin 1986). The third one (Reagan, 1985) performed according to out-dated standards was disregarded.

 

In the study of Hoff (1999), the substance was applied undiluted to the skin of 3 New-Zealand White albino rabbits and held in contact for 4 hours by means of a semi-occlusive dressing. Erythema was barely perceptible to slight at 60 minutes and 24 hours following patch removal and absent to slight at 48 and 72 hours and on day 7. Edema was absent to barely perceptible at 60 minutes following patch removal, absent to slight at 24 hours and absent to barely perceptible at 48 and 72 hours and on day 7. Mean scores for erythema, eschar formation, and edema, were less than 2 (excepting for one animal: a mean score of 2 for erythema and eschar formation was recorded). TBEC was therefore shown to be slightly to moderately irritating to rabbit skin.

 

The same conclusion was obtained in the study of Thouin (1986), where all mean scores were less than 2 excepting for one animal (mean score of 2 only for erythema).

 

Eye irritation:

Two GLP guideline study are available for this endpoint. Nevertheless Thouin study is Klimisch 1 and is therefore used as key study.

In this study, all mean score for iris were 0, mean scores for corneal opacity were between 0 and 0.3; mean scores for redness of the conjunctiva were between 0.3 and 1; and mean scores for chemosis were between 0 and 0.3.

 

In the study of Reagan (1985), mean scores calculated for each animal over 24, 48 and 72 hours were (0) (0) and (0) for cornea, iris and redness of the conjunctiva scores.

 

Regarding these results, TBEC is considered as slightly irritating when administered by ocular route to rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP OECD study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals were received from Ace Animals, Boyertown, PA on 5/18/99
The pretest body weight range was 2.3-2.7 kg.
The animals were born the weeks of 2/28 through 3/21/99
The animals were identified by cage notation and a uniquely numbered metal eartag and housed 1/cage in suspended wire cages.
Bedding was placed beneath the cages and changed at !east three times/week
Fresh Purina Rabbit Chow (Diet #5321) was provided daily. Water was freely available. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled (68 - 72°F) with a humidity range of 57- 72%, had a 12 hour light/dark cycle, and was kept clean and vermin free.

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL (undiluted)

Duration of treatment / exposure:
4 hours
Observation period:
Until 7 days after removal of the patch
Number of animals:
3
Details on study design:
The test article was placed under a 2.5 x 2.5 cm, 4 ply, surgical gauze patch
The patch was secured with non-irritating tape. The torso was wrapped with plastic in a semi-occlusive manner and secured with non-irritating tape which completely covered the plastic. Residual test article was removed from the test site by gentle washing with distilled water at the end of the exposure period, prior to scoring fur dermal reactions.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4

Body Weight observations:

R.abbitEartag:

F2084

F2103

F2106

Sex:

Pre test Body Weight-kg

F

2.7

F

2.3

F

-2.6

72 Hour Body Weight-kg

2.7

2.4

2.5

Tenninal Body Weight-kg

2.8

2.8

2.7

Erythema and escar scores:

R.abbitEartag:

F2084

F2103

F2106

60 minutes

2

2

1

24 hours

2

2

1

48 hours

1

2

0

72 hours

0

2

0f

7 days

0

2

0f

f: flaking skin

Edema scores:

R.abbitEartag:

F2084

F2103

F2106

60 minutes

1

1

0

24 hours

1

2

0

48 hours

0

1

0

72 hours

0

1

0

7 days

0

1

0

Interpretation of results:
GHS criteria not met
Conclusions:
The substance TBEC elicited slight skin irritation in an OECD 404 test, but doesn't need to be classified as irritating to skin, according to EU regulation, since mean scores for erythema, eschar formation, and oedema, are less than 2 (only one animal with a mean score of 2 for erythema and eschar formation).
Executive summary:

The acute dermal irritation potential of TBEC was evaluated in rabbits according to OECD 404 guideline . The substance was applied undiluted to the skin of 3 New-Zealand White albino rabbits and held in contact for 4 hours by means of a semi-occlusive dressing.

Oedemal reactions were scored at 60 minutes after removal of wrappings. Reactions were scored again at 24, 48 and 72 hours and on day 7 following patch removal.The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these timeperiods. Bodyweights were recorded pre-test, 72 hours and at termination.

Mean scores for erythema, eschar formation, and oedema, were less than 2 (excepting for one animal: a mean score of 2 for erythema and eschar formation was recorded).Erythema was barely perceptible to slight at 60 minutes and 24 hours following patch removal and absent to slight at 48 and 72 hours and on day 7. Edema was absent to barely perceptible at 60 minutes following patch removal, absent to slight at 24 hours and absent to barely perceptible at 48 and 72 hours and on day 7.

There were no abnormal physical signs noted during the observation period.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals weere obtained from the Broekman institute, Someren, The Netherlands.
Animals were marked with ear label and were individually housed in metal cages.
Quarantine p/acclimatizationeriod : 7 days
Date of the arrival: dec 9, 1985
Fodd and water ad libitum
Temperature 19-20 °C
Humidity 35-80 %
12 hours light, 12 hours dark
One day before administration, the fur of the animals was remoed by clipping
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
10 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used:lexible bandage


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4

  Observation time after exposure Erythema score Oedema score Mean erythema score (24/48/72 hours) Mean Oedema score (24/48/72 hours)
Rabbit 1 1 h 1 1 2 1
  24 h 2 1
  48 h 2 1
  72 h 2 1
  10 days 0 0
Rabbit 2 1 h 1 1 1,66 0
  24 h 2 0
  48 h 2 0
  72 h 1 0
  10 days 0 0
Rabbit 3 1 h 1 0 1 0
  24 h 1 0
  48 h 1 0
  72 h 1 0
  10 days 0 0
Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
The substance TBEC elicited slight skin irritation in an OECD 404 test, but doesn't need to be classified as irritating to skin, according to EU regulation; regarding mean scores for erythema and oedema.
Executive summary:

The acute dermal irritation potential of TBEC was evaluated in rabbits according to OECD 404 guideline. The substance was applied undiluted to the skin of 3 New-Zealand White albino rabbits and held in contact for 4 hours by means of a semi-occlusive dressing.

Oedemal reactions were scored at 60 minutes after removal of wrappings. Reactions were scored again at 24, 48 and 72 hours and on day 7 following patch removal..

Slight signs of irritation were reported. Mean scores for erythema, and oedema, were less than 2 (excepting for one animal: a mean score of 2 for erythema was recorded).

There were no abnormal physical signs noted during the observation period.

In conclusion, the substance is considered as a slight irritant for rabbit skin, but doesn't need to be classified according to CLP.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman institute, Someren, The Netherlands
- Age at study initiation:
- Weight at study initiation: 7 months
- Housing: in Lurane cages
- Diet and water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 40-75
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL was applied in the conjunctival sac of the right eye, the other eye served as control.
Observation period (in vivo):
10 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing : no

SCORING SYSTEM: Draize system

TOOL USED TO ASSESS SCORE: fluorescein 2% , 24 hours after tratment. in one animal, this treatment was repeated on day 10.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0 - 0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3 - 1
Max. score:
3
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0 - 0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours

  Observation time after exposure Corneal Opacity Iris lesion Conjunctival redness Conjunctival swelling (chemosis) Mean corneal opacity (24/48/72 hours) Mean iris lesion score (24/48/72 hours) Mean Conjunctival redness score (24/48/72 hours) Mean Conjunctival swelling (24/48/72 hours)
Rabbit 1 1 h 0 0 1 1 0,3 0 0,3 0
  24 h 1d 0 1 0
  48 h 0 0 0 0
  72 h 0 0 0 0
  10 days 0 0 0 0
Rabbit 2 1 h 0 0 1 2 0 0 1 0,3
  24 h 0 0 1 1
  48 h 0 0 1 0
  72 h 0 0 1 0
  10 days 0 0 0 0
Rabbit 3 1 h 0 0 1 1 0 0 0,6 0,3
  24 h 0 0 1 1
  48 h 0 0 1 0
  72 h 0 0 0 0
  10 days 0 0 0 0

d: Fluorescein treatment revealed damage of 1 % of the corneal surface which was totally reversible for 10 days

Interpretation of results:
GHS criteria not met
Conclusions:
TBEC was very sligthly irritating when administered by ocular route to rabbits.
Executive summary:

The potential of TBEC to induce ocular irritation was evaluated in rabbits in a test similar to OECD 405 guideline.

TBEC was administered undiluted to 3 New Zealand White rabbits in the conjunctival sac of one eye. The other eye was not treated and served as control. The eyes were not rinsed after administration of the test item.

Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours and 10 days after the administration. The mean values of the scores for corneal opacity chemosis, redness of the conjunctiva, iris lesions were calculated for each animal.

Only minor signs of irritation were observed. For one animal, fluorescein treatment revealed damage of 1 % of the corneal surface which was totally reversible for 10 days.

Under these experimental conditions, TBEC was therefore very slightly irritating when administered by ocular route to rabbits.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study, comparable to OECD 405 guideline. Raw data available. Nevertheless there is few data on the substance.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Six young adult New Zealand white rabbits were obtained from LaCrosse Industries, Inc., Sche­ nectady, New York for use in this study.
All animals were individually housed in wire mesh bottom cages in an environment-controlled room.
The rabbits were provided NIH 09 Rabbit Ration (Zeigler Brothers, Gardners, PA) and water ad libitum.
Animals were identified with ear tags and color coded cage cards and acclimated a minimum of 5 days.
During this period, the rabbits were ex­amined daily with respect to their general health to assure their suitability as test animals.
Prior to test initiation, the eyes of each rabbit were examined with sodium fluorescein and an ultra­ violet lamp. Only those rabbits whose eyes were free of irritation and corneal lesions were used.

Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as a control.
Amount / concentration applied:
0.1 mL.
Duration of treatment / exposure:
After instillation into the eyes, the lids were then held together for one second and the animal was returned to its cage.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Details on study design:
The eyes were examined with fluorescein and the grade of ocular reaction for each animal was recorded at 24, 48 and 72 hours post-instillation using the Draize Scale for Scoring Ocular Lesions.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions, TBEC was not irritating to eyes.
Executive summary:

The potential of TBEC to induce ocular irritation was evaluated in rabbits in a test similar to OECD 405 guideline.

TBEC was first administered undiluted to a six New Zealand White rabbits in the conjunctival sac of one eye. The other eye was not treated and served as control. The eyes were not rinsed after administration of the test item.

Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions were calculated for each animal.

 

Mean scores calculated for each animal over 24, 48 and 72 hours were (0) (0) and (0) for cornea, iris and redness of the conjunctiva scores.

Under these experimental conditions, TBEC was therefore not irritant when administered by ocular route to rabbits.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

According to EU Regulation (EC) N0. 1272/2008 (CLP), TBEC is not classified for skin and eye irritation.