Registration Dossier

Administrative data

Description of key information

Skin: 
(1) Rabbit, shaved, undiluted test item, occlusive, 5 min, washing: corrosive, Val. 2 (non-GLP, BASF XX/36, 1970).
Eye:
(1) Rabbit, undiluted test item: irreversible effects on the eye, staphyloma, (non-GLP, non-Guideline, BASF XX/36 1970).
The undiluted test item was corrosive to the skin of rabbits, caused irreversible effects on the eye of rabbits and was reported to induce respiratory irritation.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented report which meets basic scientific principles. Acceptable with restrictions (limited documentation, only 2 animals, occlusive conditions, 72-hrs reading missing, observation period only 8 days).
Principles of method if other than guideline:
Standardized test method (BASF-Test)
Before OECD Guideline 404 was established in 1982, skin irritation was tested using an internal method (BASF test). White Vienna rabbits were used. 2 animals were treated for 1, 5, 15 minutes using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance on a patch. After the application time of 1, 5, and 15 minutes, respectively, the skin was first washed with undiluted Lutrol 9, then with an aqueous Lutrol solution (50 %). The animals were observed for 8 days and skin reactions were recorded 24, 48 hours, 5 and 8 days after treatment.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 4.1 and 2.72 kg (females)

ENVIRONMENTAL CONDITIONS
- no data
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
1, 5, 15 min
Observation period:
8 days
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing: yes (exposure 1, 5, 15 min) first with undiluted Lutrol 9, then with an aqueous Lutrol solution (50 %)
- Time after start of exposure: 1, 5, and 15 min, respectively

SCORING SYSTEM:
- Descriptive scores of the raw data have been converted to Draize numerical scores.

READINGS:
- 24 and 48 hours as well as 8 days after treatment.
Irritation parameter:
other: Necrosis
Remarks on result:
other: ≥ 5 min exposure duration led to fullthickness necrosis observed after 24 hours.
Irritation parameter:
erythema score
Remarks:
(exposure duration: 1 min)
Basis:
mean
Remarks:
(animal #1 and #2)
Time point:
other: 24 and 48 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Necrosis (parchment-like)
Irritation parameter:
edema score
Remarks:
(exposure duration: 1 min)
Basis:
mean
Remarks:
(animal #1 and #2)
Time point:
other: 24 and 48 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Remarks:
(exposure duration: 5 min)
Basis:
mean
Remarks:
(animal #1 and #2)
Time point:
other: 24 and 48 hours
Score:
2.5
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Necrosis (hard)
Irritation parameter:
edema score
Remarks:
(exposure duration: 5 min)
Basis:
mean
Remarks:
(animal #1 and #2)
Time point:
other: 24 and 48 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Remarks:
(exposure duration: 15 min)
Basis:
mean
Remarks:
(animal #1 and #2)
Time point:
other: 24 and 48 hours
Score:
2.5
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Necrosis (hard)
Irritation parameter:
edema score
Remarks:
(exposure duration: 15 min)
Basis:
mean
Remarks:
(animal #1 and #2)
Time point:
other: 24 and 48 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
1 min exposure:
on the day of application bleedings at the application side and moderate to strong redness (score 2 - 3) occured; after 24 and 48 hours: strong redness (score 3) and edema (score 2); after 5 days redness (score 3) and edema (score 3) and blotchy necrosis; at the end of the observation period parchment-like necrosis, not reversible.
5 min exposure:
on the day of application leathery necrosis was observed; after 24 and 48 hours hard necrosis with reddened edge (erythema score 2 to 3), after 5 days and at the end of the observation period hard, leathery necrosis, not reversible.
15 min exposure:
on the day of application leathery necrosis was observed; after 24 and 48 hours hard necrosis with reddened edge (erythema score 2 to 3), after 5 days and at the end of the observation period hard, leathery necrosis, not reversible.
Interpretation of results:
Category 1B (corrosive)
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to OECD guideline study. Acceptable, well documented report which meets basic scientific principles. Study was conducted before establishment of the OECD Test Guideline, but study protocol is in principle similar to OECD TG 405, with acceptable restrictions (only 50 µL instilled, only 2 animals used, observation period only 8 days).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Only 50 µL instilled, only 2 animals used, observation period only 8 days.
Principles of method if other than guideline:
Standardized test method (BASF-Test)
Before OECD Guideline 405 was established, eye irritation was tested using an internal method (BASF test). White Vienna rabbits were used. 50 µL of the test substance were applied to the conjunctival sac of one eye each in 2 animals. The saline-treated adjacent eye served as control. The animals were observed after 10 min, 1 and 3 h on the day of treatment and daily up to 8 days afterwards. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. The report describes findings after 1 and 24 hours and at the end of the observation period. For final evaluation, the findings after 48 and 72 hours from the raw data were taken into account.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.97 kg (male) and 2.99 kg (female)
Vehicle:
unchanged (no vehicle)
Controls:
other: The adjacent eye served as saline control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL
Duration of treatment / exposure:
single application
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

READING: 10 min, 1, 24, 48 and 72 h and 8 days

SCORING SYSTEM: The original BASF grading was converted into the numerical grading according to the OECD Draize system.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: staphyloma
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritant / corrosive response data:
Animal 1 exhibit white nictitating membrane 72 hours after instllation; additionally, scar formation at the eye lid and alopecia in the surrounding region.
Animal 2 exhibit purulence and grey corroded nictitating membrane 72 hours after treatment; additionally, a staphyloma after 8 days as well as crusta at the eye lid and alopecia in the surrounding region.

Table 1. Results of eye irritation study.

 

Rabbit #

Time [h]

conjunctivae 

iris

cornea

remarks 

redness

swelling

1

10 min

2

1

0

3

 

1 h

2

1

0

3

 

3 h

2

2

0

3

 

24 h

2

2

0

3

 

48 h

2

2

0

3

 

72 h

2

2

2

3

 

8 days

2

2

2

3

eyelid scar

average

2.0

2.0

0.7

3.0

 

2

10 min

2

0

0

3

 

1 h

2

0

0

3

 

3 h

0

0

0

0

 

24 h

2

2

0

0

 

48 h

2

2

0

0

 

72 h

0

2

0

0

 purulence

8 days

0

0

0

0

staphyloma

average

1.3

2.0

0.0

0.0

 

 

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

There are valid in vivo data available for the assessment of the skin and eye irritating potential of the test item.

Skin irritation

In the key study, a non-GLP dermal irritation study according to an internal protocol (BASF XX/36, 1970), two female Vienna White rabbits of 4.1 and 2.72 kg, respectively, were dermally exposed to the undiluted test item (analytical purity: no data) to an area of 6.25 cm² on the upper third of the back. Test sites were covered with an occlusive dressing for 1, 5 and 15 minutes. Readings were performed 24, and 48 hours as well as 8 days after removal of the test substance and washing of the skin. Animals were observed for 8 days. 

In animals treated for 1 min an erythema score of 3, an edema score of 2 was observed 24 and 48 hours after treatment and parchment-like necrosis was detectable at the end of the observation period. Bleedings observed on day of application are not further specified.

After treatment for 5 and 15 min, hard necrosis was observed after 24 and 48 hours.

The skin irritation study is acceptable (reliability 2), but does not satisfy the guideline requirements for a skin irritation study (OECD 404) in rabbits (limited documentation, only 2 animals, occlusive conditions, 72-hrs reading missing, observation period only 8 days).

 

In the key study, the test item is corrosive to the skin based on hard, leathery necrosis after 5 min exposure duration observed after 24 hours in both animals. After 1 min exposure duration, bleedings were observed on the day of application (no time point given), but only a parchment-like necrosis was still detectable at the end of the observation period of 8 days. No histopathological confirmation was performed. Therefore, the test item was not classified for skin irritation Cat 1 A, H314 (Causes severe skin burns and eye damage).

Eye irritation

In a non-GLP eye irritation study performed similar to OECD guideline 405, 50 µL of the undiluted substance (analytical purity: no data) was instilled into one eye each of two New Zealand White rabbits (BASF, XX/36, 1970). The adjacent eyes were treated with saline and served as control. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. Readings were performed 10 min, 1, 24, 48 and 72 hours and 8 days after treatment. The test substance induced mean scores of 2 and 1.3 for conjunctivae redness, 0.7 and 0 for iris, 3 and 0 for cornea opacity, as well as 2.0 for chemosis during the relevant reading period (24, 48 and 72 hours). There was no reversibility up to the end of the observation period of 8 days.

The eye irritation study is acceptable (reliability 2), but does not fully satisfy the guideline requirements for an eye irritation study (OECD 405) in rabbits (only 50 µL instilled, only 2 animals used, observation period only 8 days).

In the key study, the test item causes severe damage to eyes.

 

Respiratory irritation

There exists no standard test method for the assessment of respiratory irritation. In the inhalation hazard test the test item caused strong mucosal irritation to the mucous membranes of rats as observed after exposure to an atmosphere that had been saturated at 20 degrees centigrade with the volatile parts of the compound (BASF XX/36, 1970; Val. 2).

Conclusion: The undiluted test item was corrosive to the skin of rabbits, causes severe damage to the eye in rabbits and was supposed to induce respiratory irritation.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data for skin and eye irritation/corrosion are reliable and suitable for the purpose of classification under Directive 67/548/EEC. As a result the substance is considered to be classified for skin irritation (C, R34) under Directive 67/548/EEC.

 

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

The available experimental test data for skin and eye irritation/corrosion are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. As a result the substance is considered to be classified for skin irritation (Cat 1B, H314,Causes severe skin burns and eye damage) under Regulation (EC) No.1272/2008.