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Description of key information

Skin and eye irritation studies on the submission substance performed according or similar to test guidelines, have demonstrated that the compound is corrosive to skin and eyes of rabbits.

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:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (short-term test)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 1981
Deviations:
yes
Remarks:
short exposure periods (3 m/ 1 h)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach, D
- Weight at study initiation: 2.30 kg
- Housing: individually in cages of stainless steel with wire mesh walk floors, 40*51 cm
- Diet (e.g. ad libitum): Kliba 341, 4 mm, Klingenthalmuehle AG, Kaiseraugst, CH; ca. 130 g/d
- Water (e.g. ad libitum): tap water, ca 250 mL/d
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS in fully air-conditioned rooms
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
3 min, 1 h
Observation period:
72 h
Number of animals:
1
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm *2.5 cm on the upper third of the back or flanks

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with Lutrol and Lutrol/water (1:1)

SCORING SYSTEM: OECD Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3 min exposure
Time point:
other: 24 - 48 - 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: full thickness necrosis already observed after 3 min exposure
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
3 min exposure
Time point:
other: 24 - 48 - 72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
1 h exposure
Time point:
other: 24 - 48 - 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: full thickness necrosis already observed after 1 h exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
1 h exposure
Time point:
other: 24 - 48 -72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Interpretation of results:
Category 1A (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item was found to be corrosive when applied undiluted to intact skin of rabbits for either 3 minutes or one hour under semiocclusive conditions.
Executive summary:

The primary skin irritation potential of the test item was investigated similar to OECD test guideline no 404 using shorter exposure periods as described for potentially corrosive matter.

The test item (0.5 mL) was applied to the intact skin of one New Zealand White rabbit under semiocclusive conditions for either 3 minutes or one hour. The scoring of skin reactions was performed at 24, 48 and 72 hours.

Skin reactions observed after 3 minutes of exposure already revealed necrotic effects within the full thickness of skin. Moreover mean (i.e. 24 -48 -72 h reading times) erythema score of 4 (i.e. maximal possible score) as well as a mean edema score of 1 was reported. After 1 hour exposure necrosis was observed, too. Mean erythema score of 4.0 and mean edema score of 2.0 was reported. All of the described effects were not reversible within 72 hours. Due to the severity of effects and irreversibility seen the test item was regarded as corrosive to skin of rabbits.
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
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to guidelines /standards
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: one additional animal
Qualifier:
according to guideline
Guideline:
other: DRAIZE test published in "Appraisal of the safety of chemicals in foods and cosmetics" Association of Food and Drug Officials of the United States, published by the Editorial Committee, Baltimore (1959), p. 46
Deviations:
no
GLP compliance:
no
Remarks:
study performed before GLP statement
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2 to 2.6 kg
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Substance application was performed once, without any washing subsequently.
Observation period (in vivo):
7 days (Ocular reactions were observed at 1hour, 24, 48 and 72 hours after the instillation and then at days 7.)
Number of animals or in vitro replicates:
4
Details on study design:
SCORING SYSTEM: according to OECD TG 405 (Draize scale), reading at 1 h, 1, 2, 3, 4 and 7 days after removal of test item

The test item was instilled into the lower conjunctival sac of the left eye of each test animal.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24,48 and 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days post application
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24,48 and 72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks:
within 7 days post application
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
other: 24,48 and 72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks:
within 7 days post application
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24,48 and 72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days post application
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24,48 and 72 h
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days post application
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24,48 and 72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days post application
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: 24,48 and 72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days post application
Irritant / corrosive response data:
Within 2 days post instillation the reading of all characteristics (i.e. corneal opacity, iris, conjunctivae redding, chemosis) resulted in maximum scores (see above), which were not reversible within 7 days post application.
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions tested the test item was corrosive to eyes.
Executive summary:

The primary eye irritation potential of the test item was investigated similar as described in OECD testing guideline no 405. The test item (0.1 g) was applied into the lower left conjunctival sac of the intact eye of four New Zealand White rabbits. Reading times were 1 h, 1, 2, 3, 4 and 7 days post instillation. Within 2 days post instillation the reading of all characteristics (i.e. corneal opacity, iris, conjunctivae redding, chemosis) resulted in maximum scores, which were not reversible within 7 days post application.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The primary skin irritation potential of the test item was investigated similar to OECD test guideline no 404 using short exposure periods as described for potentially corrosive matter.

The test item (0.5 mL) was applied to the intact skin of one New Zealand White rabbit under semiocclusive conditions for either 3 minutes or one hour. The scoring of skin reactions was performed at 24, 48 and 72 hours.

Skin reactions observed after 3 minutes of exposure already revealed necrotic effects within the full thickness of skin. Moreover mean (i.e. 24 -48 -72 h reading times) erythema score of 4 (i.e. maximal possible score) as well as a mean edema score of 1 was reported. After 1 hour exposure necrosis was observed, too. Mean erythema score of 4.0 and mean edema score of 2.0 was reported. All of the described effects were not reversible within 72 hours. Due to the severity of effects and irreversibility seen the test item was regarded as corrosive to skin of rabbits (BASF, 1990).

Other reliable short term studies supported the finding that the test item revealed corrosive characteristics when applied undiluted to intact skin of rabbits for either 3 minutes or one hour under semiocclusive conditions. (BASF, 1985 (short term), 1958).

Moreover studies using longer exposure periods found comparable results (BASF, 1985; IFREB, 1978; Younger Labs, 1972).

For example the test item (0.5 mL) was applied to the intact skin of three New Zealand White rabbits under semiocclusive conditions for four hours. The scoring of skin reactions was performed 30 to 60 minutes after removal of the test item and 24, 48 and 72 hours after start of exposure.

Skin reactions observed were necrosis of full thickness of skin already 30 to 60 minutes after patch removal. Moreover a mean (i.e. 24 -48 -72 h reading times and all animals) erythema score of 4.0 as well as an edema score of 1.33 was reported. Therefore the test item was regarded as corrosive to skin of rabbits (BASF, 1985).

In another study the test item was found also to be corrosive when applied undiluted to intact skin of male and female rabbits for four hours under semiocclusive conditions (Younger Lab, 1972).

The primary eye irritation potential of the test item was investigated similar as described in OECD testing guideline no 405. The test item (0.1 g) was applied into the lower left conjunctival sac of the intact eye of four New Zealand White rabbits. Reading times were 1 h, 1, 2, 3, 4 and 7 days post instillation. Within 2 days post instillation the reading of all characteristics (i.e. corneal opacity, iris, conjunctivae redding, chemosis) resulted in maximum scores, which were not reversible within 7 days post application (IFREB, 1978).

Another study supported these findings using a test scheme slightly differing from OECD TG no.405 (i.e. lower application volume 0.05 microlitres instead of 0.1 microlitres, 72 h reading is missing) to investigate primary eye irritation in rabbits. Under the conditions applied the test item revealed corrosive characteristics as well (BASF, 1958).


Justification for selection of skin irritation / corrosion endpoint:
Most suitable study record available for this endpoint.

Justification for selection of eye irritation endpoint:
Most suitable study record available for this endpoint.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to the results of available data the submission substance fulfills the criteria to be classified as skin corrosive substance following criteria of Regulation (EC) No. 1272/2008 (CLP) as well as Council Directive 67/548/EEC (risk phrase 35). Using the most conservative results as reported in the key study the submission substance has to be classified in subcategory 1A (CLP).

According to the results of available data the test item fulfills the criteria to be classified to cause irreversible damage to the eyes (Cat. 1) following the criteria of Regulation (EC) No. 1272/2008 (CLP). Based on the criteria set in Council Directive 76/548/EEC the submission substance as to be classified as Irritant, which causes serious damage to eyes (R41).