Registration Dossier

Administrative data

Description of key information

To evaluate the primary irritation potential of the test article, skin or eyes of New Zealand rabbits were treated with the test substance and reactions were observed and scored up to 72h (OECD guideline 404 and 405). Application onto skin did not cause irritation. In contact with eyes, slight reactions were observed which were fully reversible within 72h.

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:
1992-07-09 - 1992-08-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach/Riss, Germany
- Weight at study initiation: 2320 - 2430 g
- Housing: Individually in metal cages
- Diet: Standard diet, ad libitum
- Water: Fresh water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3 °C
- Humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day

IN-LIFE DATES: From: 1992-07-21 To: 1992-07-24
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: patches moistened with distilled water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g/animal
Duration of treatment / exposure:
4 hours
Observation period:
3 days
Number of animals:
3 (female rabbits)
Details on study design:
TEST SITE
An area of at least 36 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm²) bearing 0.5 g of the test item was applied to the right flank of each animal. A control gauze patch was applied to the contralateral flank. The patches were loosely covered with an aluminum foil (approx. 36 cm²) and held in place for 4 hours by an adhesive tape, followed by removal of the gauze patches.

SCORING SYSTEM:
The skin reaction was assessed according to the OECD scoring system at 1, 24, 48 and 72 hours intervals (after the removal of the gauze patches).

Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4

The body weight gain of all rabbits was similar. No acute clinical symptoms were observed in the animals during the test period, and no mortality occurred.

Interpretation of results:
GHS criteria not met
Executive summary:

In a primary dermal irritation study three New Zealand White rabbits were dermally exposed to 0.5 g test item (as described in section 1.2). Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 3 days and the irritation was scored at 1, 24, 48, and 72 hour(s). In this study, no signs of dermal irritation were observed. Thus, the test item was not irritating to the rabbit skin under the conditions of this study.

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:
1992-07-27 - 1992-10-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
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: Dr. K. Thomae GmbH, Biberach/Riss, Germany
- Weight at study initiation: 2460 - 2590 g
- Housing: Individually in metal cages
- Diet: Standard diet, ad libitum
- Water: Fresh water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3 °C
- Humidity: 30 - 70 %
- Photoperiod: 12 hours light cycle day

IN-LIFE DATES: From: 1992-08-04/1992-09-08 To: 1992-08-07/1992-09-11
Controls:
other: untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL (24 mg) test substance/animal
Duration of treatment / exposure:
> 24 h
Observation period (in vivo):
3 days
Number of animals or in vitro replicates:
3 (female rabbits)
Details on study design:
TREATMENT
- On test day 1, 24 mg of the test item was placed into the conjunctival sac of the left eye of each animal, after gently pulling the lower lid away from the eyeball. The lids were then held together for about one second to prevent loss of the test item. The right eye remained untreated and served as a control.

REMOVAL OF TEST ITEM
- Washing: no, eyes were not rinsed

SCORING SYSTEM:
- The eyes of each animal were examined 1, 24, 48 and 72 hours after administration. The irritant/corrosive potency of the test item was classified according to the numerical scoring system given in OECD TG 405.

TOOL USED TO ASSESS SCORE: slit-lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 1 hour
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 1 hour
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 24 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 1 hour
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No corrosion of the cornea was observed at any of the measuring Intervals.

The body weight gain of all rabbits was comparable. No acute clinical symptoms were observed in the animals during the test period, and no mortality occurred.

Interpretation of results:
GHS criteria not met
Executive summary:

In a primary eye irritation study, 24 mg (0.1 mL) of the test item (as described in section 1.2) was instilled into the conjunctival sac of the left eye of three New Zealand White rabbits. Eyes were not rinsed after application. Animals were then observed for 3 days and the irritation was scored. Minimal conjunctival redness (score 1), minimal conjunctival swelling (score 1), and minimal iris reaction (score 1) was observed in some test animals at the one-hour reading, fully reversible within 24 hours (iris reaction, conjunctival swelling) and 48 hours (conjunctival redness). No further signs of eye irritation were noted throughout the test. In this study, the test item is not an eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Procedure and observations

 

The skin irritation potential of the test substance was evaluated in two studies.

In the first study, primary skin irritation properties of the test material were investigated by topical application of 0.5 g onto shaved flank skin of each of three New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours (OECD guideline 404) (Ciba 1992c). Scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing.The second study was performed under similar conditions (0.5g for 4h onto shaved skin covered by an occlusive dressing) and with one animal only (Ciba 1991a). The test material did not provoke skin irritation or skin reactions in any of the studies.

The eye irritation potential of the test article was investigated by instillation of 24 mg (0.1 ml) into the left eye of a young female rabbit (Ciba 1992d). After observation of slight reactions, two further female rabbits were added to the treatment group. The treated eyes were not rinsed after application. Animals were observed for three days and scoring of irritation effects was performed 1, 24, 48 and 72 hours after test article application. Minimal conjunctival redness (score 1), minimal conjunctival swelling (score 1), and minimal iris reaction (score 1) was observed in some test animals at the one-hour reading, fully reversible within 24 hours (iris reaction, conjunctival swelling) and 48 hours (conjunctival redness). No further signs of eye irritation were noted throughout the test. Another study was performed under similar conditions (0.1 ml into the left eye and subsequently observed for 3d with scoring at 1, 24, 48 and 72h after treatment) with one rabbit only (Ciba 1991b). Slight redness (score 1.33) and chemosis (score 0.33) was seen 1h after installation. All effects were reversible within 72h.

 

Discussion

Application of the test substance onto skin did not cause corrosion or irritation. Administration of the test article into the conjunctival sac of the rabbit eye induced slight erythema and swelling. All reactions were fully reversible within 72h.

The test substance is considered to be as non-irritating to skin or eyes.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified as irritating for skin or eyes under Directive 67/548/EEC, as amended for the 30th time in Directive 2008/58/EC.

                                             

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

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 irritation under Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC 944/2013.