Registration Dossier

Administrative data

Description of key information

Based on the available studies the substance is severely irritating to rabbit skin and corrosive to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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: Adequate details however 24 hour exposure; no COA; non-GLP. Needs test article id statement
Qualifier:
equivalent or similar to guideline
Guideline:
other: USA Federal Hazardous Substances Act (US-FHSA),
Deviations:
not specified
Principles of method if other than guideline:
USA Federal Hazardous Substances Act (US-FHSA),
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
None provided.
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
24 and 72 hours after application
Number of animals:
Six rabbits are treated on intact ski and six on abraded skin
Details on study design:
Twelve healthy adult New Zealand White albino rabbits are used for 1-4 test substances. Twenty four hours prior to applying the materials, hair is removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions.
An amount of 0.5 ml of the test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances.
Six rabbits are treated on the intact skin, the other six on the abrades. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or the product bleeding.
After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize (J. Pharmacol. 82 (1944) 377-390). A second reading is made 48 hours later (72 hours after application).
In the case of surface active test substances the skin reactions after 72 hours usually consist of scaliness and/or necrosis,. Since the Draize grading system does not comprise these abnormalities the second reading is carried out on the basis of the laboratory's own grading system.

Irritation parameter:
overall irritation score
Remarks:
Erythema plus edema
Basis:
other: average
Time point:
other: 24
Score:
6.7
Max. score:
8
Reversibility:
no data
Remarks on result:
other: intact skin
Irritation parameter:
overall irritation score
Remarks:
erythema
Basis:
other: average
Time point:
other: 72 hours
Score:
2
Max. score:
8
Reversibility:
no data
Remarks on result:
other: intact skin
Irritation parameter:
overall irritation score
Remarks:
erythema and edema
Basis:
other: average
Time point:
other: 24 hours
Score:
6.8
Max. score:
8
Reversibility:
no data
Remarks on result:
other: abraded skin
Irritation parameter:
overall irritation score
Remarks:
erythema
Basis:
other: average
Time point:
other: 72 hours
Score:
2
Max. score:
8
Reversibility:
no data
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
After 24 hours: distinct ischemia and slight or moderate edema.
After 72 hours: very slight to distinct scaliness or incrustation.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
The test substance is a severe to very severe primary skin irritant.
Executive summary:

The test article was evaluated for its potential skin irritation potential. The test article was applied to the intact and abraded skin of rabbits for 24 hours and the reactions scored according to the Draize method 24 and 72 hours following application.

The test article was severely irritating to rabbit skin.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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: Adequate details; no COA; non-GLP. Needs test article id statement
Qualifier:
equivalent or similar to guideline
Guideline:
other: FDA - Draize Test
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
None provided.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
One tenth of a milliliter
Observation period (in vivo):
The eyes are examined at 24, 48, 72 hours and 7 days after instillation of the test material.
Number of animals or in vitro replicates:
one
Details on study design:
The eyes of the animals are examined before testing and only those animals without observable eye defects are used. On tenth of a milliliter of the test substance is allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing to prevent loss of material. The other eye remaining untreated serves as a control. The eyes are not washed following installation and the animals are released immediately.

The eyes are examined at 24, 48, 72 and 7 days after instillation of the test material.

An animal is considered as giving a positive reaction if there is, at any of the readings, discernible opacity of the cornea (other than a slight dulling of the normal lustre), or ulceration of the cornea, or inflammation of the iris (other than a slight deepening of the folds (rugae) or a slight circumcorneal injection), or if such substances produce in the conjunctivae (palpebral and bulbar, excluding the cornea and iris) an obvious swelling with partial eversion of the lids, or a diffuse deep-crimson red with individual vessels not easily discernible. The FDA scoring scale was used.

Ocular reactions are read using a binocular magnifying glass. The diagnosis of corneal damage is confirmed if necessary by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eyes are examined in a dark room under ultraviolet illumination.

A substance which has elicited corneal and/or iris lesions which have not cleared by the seventh day reading, is considered a severe eye irritant.


Irritation parameter:
cornea opacity score
Basis:
animal: only one animal used
Time point:
other: 24-hrs after instillation
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
after 7 days
Irritation parameter:
iris score
Basis:
animal: only one animal used
Time point:
other: 24 hours
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks:
after 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: only one used
Time point:
other: 24 hours
Max. score:
3
Reversibility:
not reversible
Remarks:
after 7 days
Remarks on result:
other: conjunctivae were necrotic
Irritation parameter:
chemosis score
Basis:
animal: only one used
Time point:
other: 24 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
after 7 days
Irritation parameter:
cornea opacity score
Basis:
animal: only one used
Time point:
other: 48 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
after 7 days
Irritation parameter:
iris score
Basis:
animal: only one used
Time point:
other: 48 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: only one used
Time point:
other: 48 hours
Max. score:
3
Reversibility:
not reversible
Remarks:
after 7 days
Remarks on result:
other: conjunctivae were necrotic
Irritation parameter:
chemosis score
Basis:
animal: only one used
Time point:
other: 48 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
after 7 days
Irritation parameter:
cornea opacity score
Basis:
animal: only one used
Time point:
other: 72 hours
Score:
>= 3 - <= 4
Max. score:
4
Reversibility:
not reversible
Remarks:
after 7 days
Irritation parameter:
iris score
Basis:
animal: only one used
Time point:
other: 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: i
Irritation parameter:
conjunctivae score
Basis:
animal: onnly one used
Time point:
other: 72 hours
Max. score:
3
Reversibility:
not reversible
Remarks:
after 7 days
Remarks on result:
other: conjunctivae were necrotic
Irritation parameter:
chemosis score
Basis:
animal: only one used
Time point:
other: 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
after 7 days
Irritation parameter:
cornea opacity score
Basis:
animal: only one used
Time point:
other: 7 days
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
after 7 days
Irritation parameter:
iris score
Basis:
animal: only one used
Time point:
other: 7 days
Remarks on result:
other: iris not discernable
Irritation parameter:
conjunctivae score
Basis:
animal: only one used
Time point:
other: 7days
Max. score:
3
Reversibility:
not reversible
Remarks:
after 7 days
Remarks on result:
other: conjunctivae were necrotic
Irritation parameter:
chemosis score
Basis:
animal: only one used
Time point:
other: 7 days
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
after 7days
Irritant / corrosive response data:
Moderate to complete corneal opacity, slight iritis,
necrosis of the conjunctivae and swelling with lids
about half closed.
The ocular lesions suggested permanent blindness.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test article caused very severe irreversible eye damage.
Executive summary:

The test article was evaluated for potential eye irritation. One tenth of a milliliter was instilled into one eye of one rabbit. Reactions were evaluated at 24,48, 72 hours and 7 days following instillation.

The test article induced very severe irreversible eye damage.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the available studies the substance is severely irritating to rabbit skin and corrosive to the eye. The harmonized classification for the substance is corrosive to skin and eye, category 1b and 1, respectively.