Registration Dossier

Administrative data

Description of key information

Based on the finding in an in vivo skin irritation study with rabbits and a dermal acute toxicity study with rats, in which skin reactions were scored too, the subatcne is considered a skin irritant. Results from an in vivo eye irriation study in rabbits do indicate serious eye irritation, showing slight recovery during the observation period, considered indicating reversibility. Thus, the substance is considered a sereious eye irritant.

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
Study period:
1977
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
equivalent or similar to
Guideline:
other: Draize, John H.: Dermal toxicity, "Appraisal of the safety of chemicals in foods, Drugs and Cosmetics", Association of food and drug officials of the US, 1959, pp 46-48
GLP compliance:
not specified
Species:
rabbit
Strain:
other: New Zealand Albino
Details on test animals and environmental conditions:
The animals were kept under observation at least 7 days prior to experimental use, during which period they were examined with respect to their general health and suitability as test animals. The animals were housed in suspended, wire bottomed steel cages and mantained on a standard laboratory diet. Food and water were offered ad libitum.
Type of coverage:
occlusive
Preparation of test site:
other: for each animal two sites were tested: one site abraded, one site intact
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL / site
Duration of treatment / exposure:
24 h
Observation period:
After treatment (24 h) the animals were observed one hour after removal of the test material and again after 72 hours
Number of animals:
6
Details on study design:
The test material was applied to the test sites on each rabbit according to the treatment procedure. Each test site was immediately occluded with a 2-inch square gauze patch which was secured with masking tape. The trunk of each animal was then wrapped with impervious plastic sheeting. The wrap held the patches in position and retarded evaporation of the test material during the 24 hour exposure period.
At the end of the 24 hours the plastic wrappings and patches were removed. In addition, all residual test material was removed by rinsing the test sites with lukewarm tap water (or a suitable solvent) and gentle rubbing. One hour after removal of the test material, each abraded and intact test site was examined and scored separately for erythema and edema on a graded scale of 0 to 4. After 72 hours the sites were again examinated and scored.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
3.3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: Abraded skin site
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: Abraded skin site
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
3.3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: abraded skin site
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: abraded skin site
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
3.3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin site
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
3.3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin site
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin site
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
2.7
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin site
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
only 24h and 72h values were reported
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
only 24h and 72h values were reported

Sites with second degree chemical burns (noted as moderate to diffuse) were given maximum irritation scores of 4 for both erythema and edema to obtain a primary irritation score.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The primary irritation score found was 6.2 out of 8 for intact skin and the substance was scored as severly irritating to intact skin.
Executive summary:

The primary irritation score found was 6.2 out of 8 for intact skin and the substance was scored as severly irritating to intact skin. A slight reduction in scores between the 24 hour and the 72 hour reading was seen, but in lack of an observation period a final assessment about reversibility cannot be made.

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
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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
Reason / purpose:
data waiving: supporting information
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
equivalent or similar to
Guideline:
other: Draize, John H.: Dermal toxicity , Apraisal of the safety of Chemicals in Foods, Drugs and cosmetics, Association of food and drug officials of the U.S., 1959, pp.49-51
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or tissues and environmental conditions:
The animals were kept under observation at least 7 days prior to experimental use, during which period they were examined with respect to their general health and suitability as test animals. The animals were housed in suspended, wire bottomed steel cages and mantained on a standard laboratory diet. Food and water were offered ad libitum.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
unlimited
Observation period (in vivo):
1, 24, 48, 72 h
7 and 14 days
Number of animals or in vitro replicates:
6
Details on study design:
The test material was instilled into the conjunctival sac of the right eye of each rabbit according to the treatment procedure. The left eye of each animal served as control. At each scoring interval the cornea, iris and palbebral conjunctiva were examined and graded for irritation and injury according to a standard scoring system. The maximum possible score at any 1 examination and scoring period was 110 points, which indicated maximal irritation and damage to all 3 ocular tissues. Zero indicated no irritation. In this scoring system, special emphasis was placed upon irritation or damage to the cornea, while less emphasis was placed upon damage to the iris and conjuctiva.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1h
Score:
1
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
1.5
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
14 d
Score:
1
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1h
Score:
1
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0.67
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Time point:
14 d
Score:
0.34
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
48 h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
14 d
Score:
3
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 h
Score:
2.17
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24 h
Score:
2.33
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
48 h
Score:
2.83
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
72 h
Score:
2.66
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
7 d
Score:
2.5
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
14 d
Score:
1
Max. score:
4

After the completion of the test, the scores were analysed and an eye irritation classification was assigned to the test material. The criteria used for assignment of the classification were the frequency, the extent and the persistence of irritation or damage which occurred to the 3 ocular tissue.

The classification was obtained by selecting the maximum mean irritation score at 1, 24, 48 or 72 hours after instillation. If the rate of dissipation of injury did not meet the requirements defined for the classification appropriate for a particular numerical score, the classification was raised by one or more levels.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The test item (H-240 Potassium salt of Diacid 1550) is classified as severely irritating. An improvement of scores during the observation period was evident, showing signs of reversibility.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Thhe substace was tested for skin and eye irritation in in vivo studies and furthermore a dermal acute toxicity study is available for assessment. Based on the findings in these studies, the substance is classified as a skin irritant, category 2 and an eye irritant, category 2, according to CLP (Regulation EC No. 1272/2008).