Registration Dossier

Administrative data

Description of key information

The substance was found to be non irritating to rabbit skin and to cause irreversible damage to rabbit eyes.

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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable study report. No purity information available.
Principles of method if other than guideline:
according to Fed. Reg. 38, No. 187, § 1500.41, 1973 (Draize test)
GLP compliance:
no
Specific details on test material used for the study:
solid
Scheckfarbstoff A.S.
Content: 100%
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Mean body weight: 2.5 - 3.5 kg
The rabbits are kept in individual cages measuring 540 x 360 x 315 mm or in restraining devices which allow the back of the animal to be treated. The animal house is ventilated (renewal of air = 12 times per hour; temperature 22°C; hygrometry 55 +/- 10%). The ear of each animal is pierced and a metal tag attached for individual identification.
200 g of food is provided per animal and day in the form of granules; water is given automatically and ad libitum.
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animal
Amount / concentration applied:
0.5 g (made into a paste immediately using 0.3 ml of water)
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
6
Details on study design:
The rabbits are clipped with a fine toothed electric clipper to bare a skin surface of 14 x 14 cm; thus, a precise cut can be achieved without irritating the skin mechanically. The animals are left to rest for 24 hours and then only those with perfectly healthy skin are chosen for the study.
The right flank is scarificed with a sterile scalpel blade, making 3 parallel superficial incisions 2 cm long and 0.5 cm apart. The incisions are epidermal and do not damage the dermis (should bleeding occur, a new animal is utilized).
The treated areas are subsequently covered with a 2 cm square gauze pad consisting of sterile, hydrophilic gauze of 4 layers. The material to be tested and the gauze pads are kept in contact with the skin by a patch consisting of a central, circular disc of 22 mm diameter with a surrounding adhesive, hypoallergenic, perforated plaster 10 mm wide.
Finally, an adhesive tape 6 cm wide is wound around the animal to complete the fixing of the patches. Care is taken so that the respiratory and abdominal movements of the animal are not restricted.
The rabbits are then placed for 24 hours in restraining devices.
After 24 hours of contact with the skin, the patches are removed. 1 hour later, the primary skin irritation index is evaluated and the animals are then put back into their individual cages. 48 hours later, a 2nd reading is made to determine the extent of any recovery (the 2 readings are performed respectively 25 and 72 hours after test substance application).
If after the last reading, any irritation is noted, the animals are maintained under observation for 1 week. On the 7th day, another reading is made, special attention to be paid to the presence of desquamation at the site of application.
The scores obtained on the intact and abraded skin - for erythema and edema respectively - are added at 25 and 72 hours.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 25 - 72 h
Score:
0.42
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 25 - 72 h
Score:
0.92
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 25 - 72 h
Score:
0.08
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 25 - 72 h
Score:
1.17
Max. score:
2
Reversibility:
not fully reversible within: 7 days in one animal
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
See attached figure for table.
Interpretation of results:
GHS criteria not met
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: Study performed comparable to OECD 405, but without rinsing, little information on test material, Non GLP. Animals were not specific-pathogen free (non SPF)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
After the first hour, no rinsing was performed although colouring by the substance interfered with scoring. Directly after applications, eyelids were moved up and down for several seconds.
Principles of method if other than guideline:
according to Fed. Reg. 38, No. 187, § 1500.42, 1973 (Draize test)

GLP compliance:
no
Specific details on test material used for the study:
solid
Scheckfarbstoff A.S.
Content: 100%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Mean body weight: 2.5 kg
The rabbits are kept in individual cages measuring 540 x 360 x 315 mm or in restraining devices. The animal house is ventilated (renewal of air = 12 times per hour; temperature 22°C; hygrometry 55 +/- 10%). The ear of each animal is pierced and a metal tag attached for individual identification.
200 g of food is provided per animal and day in the form of granules; water is given automatically and ad libitum.
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
Single treatment
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
6
Details on study design:
Single instillation into the conjunctival sac of the right eyelid; the test substance was not washed out. The eye lids were held closed for several seconds and moved gently up and down to voiding loss of the substance .
Readings are made 1 hour, 24 hours, 2 days, 3 days, 4 days and 7 days after instillation. When irritation is persistent, readings are made each week over a maximum periodof 2 weeks. If the lesions are too important and prevent the ocular observations or if the intensity of the lesions increases after 7 days, the animals are sacrificed and the eye examined macrosopically.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
1.4
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Circumcorneal injection and congestion of the iris
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
3.34
Max. score:
4
Reversibility:
not fully reversible within: within 21 days
Remarks:
Fully reversible in four rabbits, almost reversed in one animal and strong chemosis in one animal.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Days 1, 2, and 3
Score:
35
Max. score:
110
Reversibility:
other: not applicable
Remarks on result:
other: Index of Ocular Irritation

1 Hour 24 Hours 48 Hours
Range Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6 Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6 Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6
A) Chemosis 0 - 4 2 3 2 2 3 2 3 3 3 3 4 4 3 4 4 2 4 4
B) Discharge 0 - 3 2 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2
C) Redness 0 - 3 2 2 blue color 1 blue color 2 2 2 2 3 2 3 3 3 3 2 2 2
DIRECT PHOTOMOTOR REFLEX
OF PUPIL
  Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal (Permanent-myosis with preservation of direct photomotor reflex) Normal (Permanent-myosis with preservation of direct photomotor reflex) Normal Normal
Congestion of iris 0-2 1 (Cìrcumcorneal injection) 1 (Circumcorneal injection + congestion of the iris)
Opacity of cornea 0-4 3 3 3 2 3 2 2 2 2 2 2 2 3 3 2 2 2 2

72 Hours Day 4 Day 7
Range Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6 Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6 Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6
A) Chemosis 0 - 4 3 3 4 2 4 3 3 1 4 1 4 2 2 1 4 1 3 1
B) Discharge 0 - 3 2 1 2 2 3 2 1 0 2 0 1 0 0 0 1 0 2 0
C) Redness 0 - 3 3 2 3 2 2 2 1 1 3 1 3 1 1 1 2 1 2 1
DIRECT PHOTOMOTOR REFLEX
OF PUPIL
  Normal Normal (Permanent-myosis with preservation of direct photomotor reflex) Normal Normal Normal Normal (+myosis) Normal Normal (+myosis) Normal Normal Normal Normal (+myosis) Normal Normal (+myosis) Normal
Congestion of iris 0-2 1 (Circumcorneal injection + congestion of the iris) 1 (C.i.) 1 (C.i.) 1 (C.i.) 1 (C.i. + C.I.) 1 (C.i.) 1 (C.i. + C.I.) 1 (C.i.) 1 (C.i.) 1 (C.i.) 1 (C.i. + C.I.) 0 1 (C.i. + C.I.) 1 (C.i.)
Opacity of cornea 0-4 2 2 2 2 2 0 2 0 2 0 2 0 0 0 2 0 3 0

14 Days 21 Days
Range Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6 Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6
A) Chemosis 0 - 4 1 0 4 1 2 1 0 0 1 0 4 0
B) Discharge 0 - 3 0 0 1 0 2 0 0 0 0 0 2 0
C) Redness 0 - 3 0 0 1 0 1 1 0 0 0 0 2 0
DIRECT PHOTOMOTOR REFLEX
OF PUPIL
  Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
Congestion of iris 0-2 1 (C.i. + C.I.) 1 (C.i.) 1 (C.i.) 0 1 (C.i. + C.I.) 1 (C.i.) 1 (C.i.) 0 1 (C.i.) 0 1 (C.i. + C.I.) 0
Opacity of cornea 0-4 0 0 0 0 0* 0 0 0 0 0 0* 0

*Revascularization zone well defined on 1/4 of the corneal surface.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Eye irritation is difficult to evalutae because no pure sample is available. The substance is a disodium salt which is only existing in this form under extreme basic conditions, whereas under neutral pH, the free acid exists. The free acid is poorly soluble, whereas the substance (disodium salt) is readiliy soluble in water at pH >10. Commercial samples are solutions adjusted to pH 10,

A study on in-vivo eye irritation exists for a non-characterized sample of technical grade (IFREB 1978). This study showed the result "irreversible damage". No details on the composition of the solid test material is given.

The same sample was tested for skin irritation according to the US Federal register protocol (24h occlusive application of a moistened sample to both inact and abraded skin of rabbits). Findings were more pronounced for the abraded skin sites, and erythema scoring was not always possible because of the blue coloration by the test material. For intact skin, findings were reversible within the 7 -day observation period. In case of the abraded sites, one animal still showed slight local reactions. Mean scores were clearly below the classification thresholds according to GHS criteria.

Achtung - noch den BCOP mit der Spiro-Verbindung rein tun. Und den Fehler unten mit der "Free Acid" beheben.

An OECD 405 study for the free acid (CAS 51517 -45 -4) is available showing that the free acid is not irritating to eyes. This study is of interest in so far that if solutions of the disodium salt are neutralized, then the resulting free acid no longer poses a hazard for eye irritation. It is not relevant for the hazard assessment of the substance itself.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

A study on in-vivo eye irritation in six rabbits exists for a identified by trade name and chemical structure and described as being 100% of the provided chemical structure (IFREB 1978). Mean scores (24/48/72h) were 3.3 for chemosis, 1 for iris and 1.4 for cornea. Some animals still showed chemosis and congestion of iris at the end of the 21 day observation period. No findings on cornea were observed at the end of the observation period. The average values for chemosis, iris and cornea are in the range that requires classification as an irritant based on GHS criteria. Considering that the findings were not fully reversible within 21 days for all animals, the GHS criteria for a substance causing "irreversible damage" (GHS Cat 1) as layed out in Regulation (EC) No. 1272/2008, as amended for the seventh time in regulation No 2015/1221, are fulfilled.

The same sample was tested for skin irritation according to the US Federal register protocol (24h occlusive application of 0.5 g a moistened sample to both intact and abraded skin of rabbits). Both the skin and the eye irritation study are reported in the same report. Findings were more pronounced for the abraded skin sites, and erythema scoring was not always possible because of the blue coloration by the test material. Mean scores (24/48/72h) for intact skin were 0.42 for erythema and 0.08 for edema. For intact skin, findings were reversible within the 7 -day observation period. In case of the abraded sites, one animal still showed slight local reactions. Mean scores for intact skin were clearly below the classification threshold as an irritant according to GHS criteria. As a result the substance is not considered to be classified for skin irritation under Regulation (EC) No. 1272/2008,as amended for the seventh time in Regulation (EC) No 2015/1221.