Registration Dossier

Administrative data

Description of key information

The test substance is not irritating or corrosive to the rabbit skin (OECD 404, GLP). 
The test substance is not irritating to the rabbits eye (OECD 405, GLP).

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:
29 Sept. - 02 Oct. 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 13 weeks
- Weight at study initiation: 2447 - 2628
- Housing: plastic cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20 °C
- Humidity (%): 50 - 75 %
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 29. September to 02. October 1988
Type of coverage:
semiocclusive
Preparation of test site:
other: clipping
Vehicle:
water
Controls:
no
Amount / concentration applied:
Three portions of 0.5 gram of the test substance were transferred into glass vials. Prior to treatment each portion was moistened with 0.5 ml Milli-RO water. Immediately thereafter, each portion of the prepared test substance was spread on a 6 cm^2 patch of Metalline and mounted on permeable tape.
Duration of treatment / exposure:
4 hours
Observation period:
Approximately 55 min, 24 hrs; 48 hrs; 72 hrs and additionally on day 4 after removal of the patches.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approximately 10 cm x 10 cm
- Type of wrap if used: The animals were wrapped in flexible bandage

REMOVAL OF TEST SUBSTANCE
The remaining test substance was removed using a dry tissue subsequently a tissue moistened with tap-water

SCORING SYSTEM:
The exposed skin areas were examined for signs of erythema and oedema and the responses were scored (according to the grading system given in the OECD guideline 404) approximately 55 minutes, and 24, 48 and 72 hours and 4 days after removal of the patches. For reference the control site on the contralateral flank was used. In order to facilitate the scoring, the skin area concerned of all animals was shaved again at least 5 hours before observation on day 1.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean (24+48+72h)
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean (24+48+72h)
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: day 4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean (24+48+72h)
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean (24+48+72h)
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: day 4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean (24+48+72h)
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean (24+48+72h)
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: day 4

Table 1: Primary skin irritation scores

  time animal 1 animal 2 animal 3
erythema 55 min  1
24 h  0
48 h  0
72 h  0
4 d  0 0 0
edema 55 min  0
24 h  0
48 h  1
72 h  1
4 d  0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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:
03. - 10. October 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands
- Housing: plastic cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21 °C
- Humidity (%): 50 - 75
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: To: 03 - 10 October 1988
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.07 g of the test substance (corresponding to 0.1 ml)

Observation period (in vivo):
Examination of the eyes after 1 hour and 1, 2, 3, and 7 days after instillation of the test substance.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein (2% solution in water)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72h
Score:
0.77
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 48h

Table 1: Eye irritation scores of the test substance

 

time

animal 1

animal 2

animal 3

corneal opacity

24 h

0

0

0

48 h

0

0

0

72 h

0

0

0

iris

24 h

0

0

0

48 h

0

0

0

72 h

0

0

0

conjunctivae

24 h

2

1

1

48 h

1

1

0

72 h

1

0

0

chemosis

24 h

1

1

0

48 h

0

0

0

72 h

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In a primary dermal irritation study conducted according to OECD 404 and GLP, three NZW rabbits were dermally exposed to the test substance for 4 hours. Animals then were observed for three days and additional observations were made on day 4. The single semi-occlusive application elicited very slight oedema in all animals at the 48 and/or 72 hour reading, but no erythema. All reactions had resolved by day 4. The observed signs of skin irritation were not relevant for classification and labelling.

Eye irritation:

In a primary eye irritation study according to OECD TG 405 and GLP, 0.07g of the test substance was singly instilled into the rabbits eye. 24 hrs after exposure, the maximum response observed was grade 2 reddening of the eyelids of one rabbit, while the two other animals showed very slight reddening. Very slight chemosis was observed during the first 24 hours. All animals showed lacrimation in response to the test substance (maximum at 24 hours), while the treated eyes stained intensely black. No adverse effects to the cornea and the iris were observed in any of the animals during the entire observation period. Treatment of the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any corneal epithelial damage. No signs of systemic intoxication were observed in any of the rabbits. All reactions had resolved 7 days after instillation.

Justification for classification or non-classification

Based on the results of the skin and eye irritation key toxicity studies, the test substance is not subject to classification and labelling for skin irritation or eye irritation according to Directive 67/548/EEC and Regulation 1272/2008/EC.