Registration Dossier

Diss Factsheets

Administrative data

Description of key information

GLP guideline studies in rabbits are available for skin and eye irritation according to OECD 404 and OECD 405, respectively.

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:
1990-11-27 to 1990-12-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. An updated OECD guideline from 2002 is available; changes do not affect the reliability of this study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(1981)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
84/449/EEC
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, UK
- Age at study initiation: No data
- Weight at study initiation: 3.5, 3.2, and 3.6 kg, all female
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Standard diet "Ssniff K 4", approx. 100-120 g per animal and day (fed in the morning)
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): Approx. 50 %
- Air changes (per hr): Approx. 10/h
- Photoperiod (hrs dark / hrs light): 12/12 (illumination from 6 to 18 hrs CET)

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg, moistened
Duration of treatment / exposure:
4 h
Observation period:
7 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: semiocclusive dressing (Fixomull-Stretch Klebevlies, Beiersdorf no. 2293)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With water
- Time after start of exposure: 4 h

SCORING SYSTEM:
According to DRAIZE
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Other effects:
No other effects.

Skin irritant effects of the TCD-emulsifier:

Animal No.

Body weight

[kg]

Sex

Draize grade after

Irrit. index

1 h

24 h

48 h

72 h

7 d

14 d

e

o

e

o

e

o

e

o

e

o

e

o

e

o

L4

3.5

Female

0

0

0

0

0

0

0

0

0

0

-

-

0.0

0.0

L6

3.2

Female

0

0

0

0

0

0

0

0

0

0

-

-

0.0

0.0

K23

3.6

Female

0

0

0

0

0

0

0

0

0

0

-

-

0.0

0.0

e: erythema and eschar formation

o: oedema formation

-: not examined

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Irritant and/or corrosive effects of TCD-emulsifier were tested according to OECD uideline 404 and EU Method B.4. The test substance is not irritating to rabbit skin.
Executive summary:

In a primary dermal irritation study according to OECD guideline 404 and EU method B.4, adult albino rabbits (strain: HC:NZW) (3 female animals) were dermally exposed to 500 mg TCD-emulsifier in water for 4 hours, administered to 6 cm² at dorso-lateral areas of the animals' trunk. Animals then were observed for 7 days. Irritation was scored by the method of DRAIZE.

No irritation occurred. Based on the study results, TCD-emulsifier is not classified according to CLP Annex I as a dermal irritant.

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:
1990-11-27 to 1990-12-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. An updated OECD guideline 405 from 2012 is available; changes do not affect the reliability of this study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1981)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
84/449/EEC
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation:
- Weight at study initiation: 3.5, 3.2, and 3.6 kg, all female
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Standard diet "Ssniff K 4", approx. 100-120 g per animal and day (fed in the morning)
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): Approx. 50 %
- Air changes (per hr): Approx. 10/h
- Photoperiod (hrs dark / hrs light): 12/12 (illumination from 6 to 18 hrs CET)
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µl (approx. 40 mg)
Duration of treatment / exposure:
24 h
Observation period (in vivo):
7 d
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing with saline
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize Grades

TOOL USED TO ASSESS SCORE: Hand-slit lamp, fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.1
Max. score:
0.3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
Erythema
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1.2
Max. score:
1.3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.1
Max. score:
0.3
Reversibility:
fully reversible

Results for the grading of irritating effects on the eye:

Animal no./ Sex

Body weight

Tissue

Signs

DRAIZE grades

Irritation index

1 h

24 h

48 h

72 h

7 d

14 d

21 d

M26/ Female

2.7 kg

Cornea

o

0

0

0

0

0

-

-

0.0

a

0

0

0

0

0

-

-

 

Fluorescein

i

-

1

1

0

-

-

-

 

a

-

1c

1p

0

-

-

-

 

Iris

 

0

0

0

0

0

-

-

0.0

Conjunctivae

r

1

1

1

1

0

 

 

1.0

s

1

0

0

0

0

 

 

0.0

Aqueous humour

 

0

0

0

0

0

-

-

 

Discharge

 

1

0

0

0

0

-

-

 

M25/ Female

2.9 kg

Cornea

o

0

0

0

0

0

-

-

0.0

a

0

0

0

0

0

-

-

 

Fluorescein

i

-

1

1

0

-

-

-

 

a

-

2c

1c

0

-

-

-

 

Iris

 

0

1

0

0

0

-

-

0.3

Conjunctivae

r

1

2

1

1

0

-

-

1.3

s

2

1

0

0

0

 

 

0.3

Aqueous humour

 

0

0

0

0

0

-

-

 

Discharge

 

3

0

0

0

0

-

-

 

K8/ Female

3.4 kg

Cornea

o

0

0

0

0

0

-

-

0.0

a

0

0

0

0

0

-

-

 

Fluorescein

i

-

0

-

-

-

-

-

 

a

-

0

-

-

-

-

-

 

Iris

 

0

0

0

0

0

-

-

0.0

Conjunctivae

r

1

2

1

1

0

-

-

1.3

s

1

0

0

0

0

 

 

0.0

Aqueous humour

 

0

0

0

0

0

-

-

 

Discharge

 

1

0

0

0

0

-

-

 

o: Opacity

a: Area

i: Intensity

r: Redness

s: Swelling

-: Not examined

c: Confluent diffuse areas

p: Scattered punctate

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The eye irritant/corrosive potential of the test item was assessed in rabbits according to OECD guideline 405 and EU method B.5. The test substance induced slight reactions of the mucous membranes and mild corneal effects which were fully reversible within 7 days. The substance is regarded as slightly irritating.
Executive summary:

In a primary eye irritation study in accordance with OECD guideline 405 and EU method B.5, 100 µl of TCD-emulsifier was instilled into the conjunctival sac of adult rabbits (strain: HC:NZW) (3 female) for 24 hours. The eyes were rinsed with saline after 24 h of exposure. Animals then were observed for 7 days. Irritation was scored by the method of DRAIZE.

The exposure induced slight reactions of the mucous membranes and mild corneal effects which were fully reversible within 7 days. Based on the study results, the test item is not classified as an eye irritant according to CLP Annex I.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The irritant/corrosive potential of the test substance was studied on the skin and eye of the rabbit in accordance with OECD guidelines 404 and 405. Whilst considering OECD interpretation guides, the results were interpreted in conjunction with the nature, intensity, and reversibility of the responses observed.

The results indicate that the test substance can be regarded as 'not irritating to the skin'.

Administration of the test substance to the eye caused slight reactions of the mucous membranes and mild corneal effects which proved to be fully reversible within 7 days. Therefore the test substance may be considered as 'slightly irritating to the eye' but does not fulfil the criteria of the CLP regulation for classification as eye irritant.


Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The results indicate that the test substance can be regarded as 'not irritating to the skin'.

Exposure of the test substance to the eye caused slight reactions of the mucous membranes and mild corneal effects which proved to be fully reversible within 7 days. Therefore the test substance may be considered as ‘slightly irritating to the eye' but does not fulfil the criteria of the CLP regulation for classification as eye irritant.