Registration Dossier

Administrative data

Description of key information

skin: not irritating
eye: irreversible effects

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: The study is comparable to OECD Guideline 404 with acceptable restrictions (partly limited documentation, e.g. details about the test substance; exposure period 20 h and occlusive coverage conditions [worst case scenario]).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
20 h occlusive exposure
Principles of method if other than guideline:
Skin irritation was tested using an internal method (BASF test)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
One females, initial weight: 2.61 and one male, initial weight 2.84 kg
no further details
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
water
Controls:
no
Amount / concentration applied:
80% test substance (w/v) in distilled water was used. The application site was covered with an cotton patch of 2.5 X 2.5 cm; prior application of the test substance to the patch, amount not reported (presumably patch soaked with the test substance); no further data.
Duration of treatment / exposure:
1, 5, or 15 minutes or 20 h
Observation period:
Results were recorded each working day for up to 7 days. Scoring was done 24 h, 48 h and 5 and 7 days after initiation.
Number of animals:
2 rabbits
Details on study design:
After the reported exposure time, the skin was washed with 50% Lutrol in water.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24/48 h
Score:
0
Max. score:
4
Remarks on result:
other: 20 h exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24/48 h
Score:
0
Max. score:
4
Remarks on result:
other: 20 h exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24/48 h
Score:
0
Max. score:
4
Remarks on result:
other: 20 h exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/48 h
Score:
0
Max. score:
4
Remarks on result:
other: 20 h exposure
Irritant / corrosive response data:
No effects were detected after 1, 5, or 15 minutes of exposure; no effects were seen after 20 h occlusive application (see Table below).
No edema was reported in any experiment.
Other effects:
Body weight not altered.

Skin erythema in 2 rabbits after dermal exposure to the undiluted test substance for 20 h followed by washing with 50% Lutrol

Time after initiation of exposure

20 hours exposure; erythema in

Rabbit 1

Rabbit 2

24 h

0

0

48 h

0

0

5 days

0

0

7 days

0

0

Evaluation transformed to OECD-Draize scoring; no edema reported.

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The test substance has no skin irritant properties.
Executive summary:

The study is comparable to OECD Guideline 404 with acceptable restrictions (partly limited documentation, e.g. details about the test substance; exposure period 20 h and occlusive coverage conditions [worst case scenario]).

Two rabbits were dermally exposed to moistened test substance for 1, 5, 15 minutes or for 20 h. The coverage was occlusive; the skin was washed after exposure. Skin reaction was scored 24 & 48 h, and 5 and 7 days initiation. No erythema was found. No edema was reported.

Conclusion: The test substance has no skin irritant properties.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is comparable to OECD Guideline 405 with acceptable restrictions (partly limited documentation, e.g. no details about the test substance; only 50 mg instead of 100 mg test substance instilled; not washed out but comparison with talcum powder was given; max. observation period only 8 days, 21 days recommended).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(scorring system); BASF-Test
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
Two males, initial bw 3.07 or 3.17 kg
no further details
Vehicle:
unchanged (no vehicle)
Controls:
other: same amount talcum powder into the conjunctival sac of the left eye
Amount / concentration applied:
ca. 50 mg instilled into the conjunctival sac
Duration of treatment / exposure:
unwashed
Observation period (in vivo):
up to 8 days after application; see Table in the result section.
Number of animals or in vitro replicates:
2
Details on study design:
The animals were observed several times on the treatment day and up to 8 days afterwards, and findings were recorded on working days.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: observation up to day 8
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: observation up to day 8
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: observation up to day 8
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: observation up to day 8
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: observation up to day 8, score at day 8: 3
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: observation up to day 8
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: observation up to day 8
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: observation up to day 8
Irritant / corrosive response data:
Scar formation was observed at day 6 in animal #1; ciliary injection at day 6 and scar formation at day 8 was observed in animal #2.
Small effects were also detected in the left eye (talcum control; mechanical irritation): slight redness (Draize conjunctivae score 1) which was completely reversible within 6 days (animal #1) and 24 h (animal #2).
Other effects:
no effects on body weight
no further data

Eye irritation in 2 rabbits after instillation of 50 mg test substance
Scoring according to OECD-Draize scheme; description of effects from raw data

Time period after application

Rabbit 1

Rabbit 2

Erythema

1 h

1

1

24 h

2

1

48 h

2

2

72 h

1

2

6 days

1

1

8 days

0

1

Time period after application

Rabbit 1

Rabbit 2

Edema

1 h

2

1

24 h

1

2

48 h

0

2

72 h

0

2

6 days

0

1

8 days

0

1

Time period after application

Rabbit 1

Rabbit 2

Corneal opacity and other effects

1 h

1 (discharge)

1

24 h

2 (discharge)

1

48 h

2 (cornea covered by a smeary film)

2 (discharge)

72 h

2 (cornea covered by a smeary film)

2 (ulceration)

6 days

2 (scar formation)

2 (ciliary injection)

8 days

1 (scar formation)

2 (scar formation)

Raw data not clearly compatible with results described in the summary protocol

Interpretation of results:
highly irritating
Remarks:
Migrated information
Conclusions:
The instillation of 50 mg test substance into the conjunctival sac of rabbit eyes resulted in irreversible effects.
Executive summary:

The study is comparable to OECD Guideline 405 with acceptable restrictions (partly limited documentation, e.g. no details about the test substance; only 50 mg instead of 100 mg test substance instilled).

An amount of 50 mg test substance was instilled into the right eye of 2 rabbits; the left eye served as control (50 mg talcum powder instilled). Effects were recorded 1, 24, 48, 72 h and up to 8 days after instillation. Edema and corneal opacity OECD score 2 were reported in both rabbits as well as ulceration (one rabbit) and scar formation (both rabbits). Corneal opacity was still present in both rabbits 8 days after instillation.

Conclusion: The instillation of 50 mg test substance into the conjunctival sac of the rabbit eyes resulted in irreversible effects.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

SKIN:

Skin irritation was tested using an internal method (BASF test, 1974). Two rabbits were dermally exposed to moistened test substance for 1, 5, 15 minutes or for 20 h. The coverage was occlusive; the skin was washed after exposure (worst case scenario). Skin reaction was scored 24 and 48 h, and 5 and 7 days after initiation. No erythema was found. No edema was reported.

Conclusion: The test substance has no skin irritant properties.

 

EYE:

Eye irritation was tested using an internal method (BASF test, 1974). An amount of 50 mg test substance was instilled into the right eye of 2 rabbits; the left eye served as control (50 mg talcum powder instilled). Effects were recorded 1, 24, 48, 72 h and up to 8 days after instillation. Mean scores (24 -72 h of both animals) are 2 (cornea), 0 (iris), 1.7 (conjuctivae) and 1.15 (chemosis). Corneal opacity was still present in both rabbits 8 days after instillation (end of observation period).

Conclusion: The instillation of 50 mg test substance into the conjunctival sac of the rabbit eyes resulted in irreversible effects.


Effects on eye irritation: corrosive

Justification for classification or non-classification

The substance is not irritating to the skin but causes irreversible effects on the eye and is therefore classified as Xi R41 according to Annex VI of Directive 67/548/EWG and Eye Irritation Cat. 1 according to Annex I of Directive 1272/2008 (EU-GHS).