Registration Dossier

Administrative data

Description of key information

Skin irritation: Not irritating (OECD 404, GLP, Rel.1, K).
Eye irritation: Not irritating (OECD 405, GLP, Rel. 1, K).

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:
From 1992-08-24 to 1992-09-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to the original OECD Guideline 404 (1981).
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(Adopted 12th May 1981)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Thomae GmbH, Biberach-D
- Age at study initiation: approximately 19 months
- Weight at study initiation: approximately 2460 g
- Housing: individual accommodation
- Diet (e.g. ad libitum): Ssniff rabbit diet K4, Ssniff GmbH, Soest-D (Batch 550792/01) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 20-25°C
- Humidity (%): approximately 45-70%
- Air changes (per hr): at least eight per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: August 24, 1992 To: September 07, 1992
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
moistened
Controls:
other: untreated skin areas serve as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours and 7 days after exposure
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: right flank
- % coverage: ca. 6 cm²
- Type of wrap if used: adhesive air- and vapour permeable gauze-patch fixed by a hypo-allergenic adhesive gauze-bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, but no detail
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale, as described in OECD Guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Scratching was observed at 24-48-72 hours
Irritant / corrosive response data:
Slight to weak erythema and slight oedema of the first, slight erythema of the second, and no reaction of the third experimental animals were observed during the first 72 hours after exposure. One week later the first and second experimental animals were without irritation effects.
Other effects:
None

Table 7.3.1/1: Mean irritant/corrosive response data for each animal at each observation time up to removal of animals from the test

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

1 / 1 / 0

1 / 0 / 0sc

24 h

2 / 1 / 0

1 / 0 / 0sc

48 h

1 / 1 / 0

0 / 0 / 0sc

72 h

1 / 1 / 0

0 / 0 / 0sc

Average 24h, 48h, 72h

1.3 / 1.0 / 0.0

0.3 / 0.0 / 0.0

Reversibility*)

c.

c.

Average time for reversion

7 days

48 hours

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

sc = scratch

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material induces a slight to weak irritation being reversible within 7 days. Therefore the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).
Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 g of undiluted test material was moistened and applied on the shaved skin of the dorsal flank area of 3 Kleinrussen, Chbb:HM rabbits.Test sites were covered with a semi-occlusive dressing for 4 hours. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 hours and 7 days after the removal of the patch.

 

Slight to weak erythema and slight oedema of the first, slight erythema of the second, and no reaction of the third experimental animal were observed during the first 72 hours after exposure. One week later the first and the second experimental animal were without irritation effects.

The individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 1.33 / 1.00 / 0.00 for erythema and 0.33 / 0.00 / 0.00 for oedema.

 

Therefore the test material is not classified as irritant to the skin according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

 

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:
From September 22 to October 13, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to the original OECD Guideline 405 (1987).
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(Adopted February 24, 1987)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae GmbH, D-Biberach
- Age at study initiation: approximately 20 months
- Weight at study initiation: approximately 2470 g
- Housing: individual accommodation
- Diet: Ssniff rabbit diet K4 ad libitum (Ssniff GmbH, D-Soest)
- Water: tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: September 22, 1992 To: October 13, 1992
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48, 75 hours after instillation, then on Days 7and 14.
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tepid tap water
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize scale as described in the OECD guideline No. 405.

TOOL USED TO ASSESS SCORE: slit lamp microscope
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The observed conjunctival reactions of the experimental animals were weak and disappeared completely within 14 days.
Other effects:
None

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0

0 / 0 / 0

1 / 1 / 2

1 / 1 / 1

0 / 1 / 0

24 h

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

1 / 0 / 0

0 / 0 / 0

48 h

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

0 / 0 / 0

0 / 0 / 0

72 h

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

0 / 0 / 0

0 / 0 / 0

Average 24h, 48h, 72h

0 / 0 / 0

0 / 0 / 0

1.0 / 1.0 / 1.0

0.33 / 0.0 / 0.0

0 / 0 / 0

Reversibility*)

-

-

c.

c.

-

Average time for reversion

-

-

14 days

48 h

-

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material induced weak to mild irritation being reversible within 14 days. Therefore the test material is not classified as irritant to the eyes according to the criteria of the Annex I of the Regulation (EC) No. 1272/2008 (CLP).
Executive summary:

In an eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into the right eye of 3 Kleinrussen (Chbb: HM) rabbits. The eyes were rinsed 24 hours after the instillation of the test item. The left eye of each rabbit served as control. Animals were observed at 1, 24, 48 and 72 hours after dosing under a standard light source, and then on Days 7 and 14. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

The observed conjunctival reactions of the experimental animals were weak and disappeared completely within 14 days. 

 

The individual score for each individual lesion for each animal within 3 scoring times (24, 48 and 72 hrs) were 1.00/1.00/1.00 for erythema, 0.33/0.00/0.00 for chemosis and 0.00 for discharge, iris lesions and corneal opacity.

 

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Annex I of the Regulation (EC) No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Two reliable studies (reliability scores of 1) were available (Henkel, 1992; RCC, 1990), conducted according to OECD guideline No. 404 and in compliance with GLP. The study of Henkel showed the highest irritation scores and was therefore selected as the key study.

In this study, the individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 1.33 / 1.00 / 0.00 for erythema and 0.33 / 0.00 / 0.00 for oedema. All effects were fully reversed within 7 days. Under the study conditions, the substance was not a skin irritant.

The study of RCC supports this conclusion with mean scores of 0.00 / 0.00 /0.33 for erythema and 0.00 / 0.00 / 0.00 for oedema.

The last study (Biosearch, 1979, rel.3) was performed according to US-FHSA and accordingly involved a 24 -hour exposure followed by observation at 24 hour and 72 hour only. Mean scores of 1.83 and 1.00, for erythema and oedema respectively, were calculated over the 6 animals at 72 -hour. In the absence of 48 -hour scoring and based on the results from more reliable studies, the data were not considered appropriate for classification.

Eye irritation:

A key study was identified (Henkel, 1992, rel.1). In this eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, undiluted test material was instilled into the right eye of 3 rabbits. The observed conjunctival reactions of the experimental animals were weak and disappeared completely within 14 days. The individual scores for each animal within 3 scoring times (24, 48 and 72 hrs) were 1.00/1.00/1.00 for erythema, 0.33/0.00/0.00 for chemosis and 0.00 for discharge, iris lesions and corneal opacity. Under the test conditions, the substance is not an eye irritant.

This result is supported by a second study performed according to US-FHSA but pre-GLP (Biosearch, 1979, rel.2). In this study, the calculated mean scores for all 6 animals within 3 scoring times (24, 48 and 72 hrs) were as follows: 0.55 for cornea opacity, 2.22 for area involved, 0.55 for iris lesions, 1.39 for redness, 1.55 for chemosis and 2.11 for discharge. Discharge score of 1 was still observed at the end of the observation period (7 days) in 1 animal but is expected to reverse within a standard period of 21 days.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 .

Self classification:

Based on the available data no additional self-classification is proposed regarding both skin and eye irritation according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP).

No data was available on respiratory irritation, however the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation.