Registration Dossier

Administrative data

Description of key information

Skin irritation was tested in a guideline study according to OECD guideline 404 in rabbits. No severe signs of irritation occurred during the whole observation period. No clinical signs of systemic toxicity were observed. In conclusion, testing for primary dermal irritation in the rabbit showed that the test substance is not irritating.

According to OECD guideline 405 an amount of 100 mg of the test item was administered to the conjunctival sac of the left eye of three female New Zealand White rabbits. The treated eyes were washed out 24 h after the administration of the test substance. The untreated eyes served in each case as control. The test substance caused no severer irritating effects in the eyes of the animals.

No clinical signs of systemic toxicity were observed. In conclusion, the testing for eye irritation in rabbits showed that the test substance is not irritating to the eyes.

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:
June - July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Adopted April 24, 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Adopted July 31, 1992
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Kißlegg, Germany
- Weight at study initiation: 2.29 - 2.59 kg
- Housing: in fully air-constioned rooms in spearate cages arranged in a battery
- Diet (e.g. ad libitum): ssniff K-H (V2333), ad libium and hay (approx. 15 g daily)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 week under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 24. June To: 4. July 2003
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: Tylose
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g pasted with 0.5 mL tylose

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL tylose
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100%
- Type of wrap if used: semi-occlusive bandage

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

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
30-60 min, 24, 48 and 72 h

SCORING SYSTEM:
according to Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
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
Irritant / corrosive response data:
30-60 min. after decontamination the animals showed very slight erythema. 24 h after decontamination al signs of irritation had disappeared.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the in vivo dermal irritation stduy in rabbits the test substance is not skin irritating.
Executive summary:

Three female New Zealand White rabbits were tested for skin irritation with 0.5 g of the test substance moistened with 0.5. mL tylose after an exposure period of 4h. No severe signs of irritation occurred during the whole observation period. No clinical signs of systemic toxicity were observed. In conclusion, testing for primary dermal irritation in the rabbit showed that the test substance is not irritating.

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:
July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Adopted April 24, 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Adopted July 31, 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Kißlegg, Germany
- Weight at study initiation: 2.79 - 3.99 kg
- Housing: in fully air-conditioned rooms in separate cages
- Diet (e.g. ad libitum): ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 week under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 8. July To: 22. July 2003
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

VEHICLE
none
Duration of treatment / exposure:
24 h
Observation period (in vivo):
examinations:
1, 24, 48 and 72 h after administration
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 24 h after administration the treated eye was washed out thoroughly with isotonic saline at approx. 37°C
- Time after start of exposure: 24 h

SCORING SYSTEM:
According to Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
1 h uup to 72 h after administration the animals showed definitely injected blood vessels up to diffuse crimson color and up to 48 h after administration very slight up to obvious swllings with partial eversion of lids. One animal showed slightly reddened iris 24 h up to 48 h after administration. 1 h up to 24 h after administration the animals showed serious eye discharge discolored by the compound. 7 days after administration all signs of irritation had disappeared.
Interpretation of results:
GHS criteria not met
Conclusions:
The testing of the test item for primary eye irriation in the rabbit led to the conclusion that the substance is not irritating.
Executive summary:

An amount of 100 mg of the test item was administered to the conjunctival sac of the left eye of three female New Zealand White rabbits. The treated eyes were washed out 24 h after the administration of the test substance. The untreated eyes served in each case as control. The test substance caused no severer irritating effects in the eyes of the animals.

No clinical signs of systemic toxicity were observed. In conclusion, the testing for eye irritation in rabbits showed that the test substance is not irritating to the eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation: 1 key study available: not irritating

Eye irritation: 1 key study available: not irritating

 

There is one reliable study on the skin irritancy potential. Skin irritation was tested in a guideline study according to OECD guideline 404 in New Zealand White rabbits. No severe signs of irritation occurred during the whole observation period. No clinical signs of systemic toxicity were observed. In conclusion, testing for primary dermal irritation in the rabbit showed that the test substance is not irritating.

There is one reliable study available on the eye irritancy potential. The test substance caused no severer irritating effects in the eyes of the animals.

No clinical signs of systemic toxicity were observed. In conclusion, the testing for eye irritation in rabbits showed that the test substance is not irritating to the eyes.

Justification for classification or non-classification

With reference the reported scores HPP Additive D11 does not have to be classified as irritant to the skin and eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).