Registration Dossier

Administrative data

Description of key information

Not skin and eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
other: experimental study on similar substance
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: different data report by Colipa
Qualifier:
according to
Guideline:
other: Different guidelines followed
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
other: intact and scarified
Vehicle:
other: unchanged and water or hydropylic cream preparation
Controls:
yes, concurrent no treatment
Amount / concentration applied:
1° Test: dye was applied at doses of 0.316, 1, 4, 3.16 and 10 g/kg
2° Test: dye was applied in a solution of 0.1, and 1% in water or hydrphylic cream preparation
Duration of treatment / exposure:
1° Test: no data
2° Test: repeated application for intact skin: 5 times a week for 13 weeks; for scarified skin: 5 times a week for 3 weeks
Number of animals:
1° Test: 4 animals for group
2° Test: 7 animals for group (intact skin); 2 animals for group (scarified skin)
Irritation parameter:
other: irritant effect
Basis:
mean
Time point:
other: after 13 weeks
Score:
ca. 0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
The tested substance is not irritant for skin.
Executive summary:

In the first test, no irritant effects were seen on rabbit skin.

In the second test, slight to moderate irritation was noted but clinical invenstigation did not reveal any substance related effects.

Based on the test results, the tested substance is not to be considered as irritant for skin.

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
other: experimental study on similar substance
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: published report with many details on results
Qualifier:
equivalent or similar to
Guideline:
other: in vivo test on rabbits
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three rabbits, weighing two to three kilograms, are used for each assay. Animals are housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals are maintained on a 12-hour light and 12-hour dark cycl
Type of coverage:
open
Preparation of test site:
not specified
Vehicle:
other: propylene glycol
Controls:
yes, concurrent no treatment
Amount / concentration applied:
1 ml of 10% solution
Duration of treatment / exposure:
spread daily for 5 days of the week for two weeks
Number of animals:
three rabbits
Details on study design:
Follicular keratosis is judged both macroscopically (visually) and microscopically with a micrometer to measure the width of the follicular keratosis. The macroscopic response is determined by averaging the measurements of the width of six follicles using a Mitutoyo Dial Micrometer (#536-724). A similar microscopic micrometer measurement is obtained by averaging the width of six follicles under a magnification of 430 x after a 6-ram biopsy specimen is fixed in formalin, sectioned at six microns, and stained with hema- toxylin-eosin.
The results are then combined on a scale of one to five.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: not specified
Score:
ca. 0
Max. score:
5
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The tested substance irritation grade was found to be 2 and based on the irritation scale, there was diffuse scaling but no erythema.
Interpretation of results:
GHS criteria not met
Conclusions:
The tested substance is not irritant for skin.
Executive summary:

Based on the test results, the tested substance does not show irritating effect on rabbits ears skin.

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
other: experimental study on similar substance
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Toxnet reference - Jefca Evaluation
Qualifier:
no guideline available
Principles of method if other than guideline:
application of five days a week for more than 13 weeks
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
other: abraded and intact skin
Vehicle:
other: in water or as a hydrophilic ointment
Controls:
not specified
Amount / concentration applied:
500 g/kg
Duration of treatment / exposure:
3 weeks for abraded skin and 13 weeks for intact skin
Number of animals:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: no data
Score:
0
Max. score:
5
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No compound-related effect on general appearance, body weight, clinical laboratory studies and gross and microscopic pathology. No dermal irritation was noted, except that produced by the hydrophilic ointment base
Interpretation of results:
GHS criteria not met
Conclusions:
The tested substance is not a skin irritant.
Executive summary:

Based on the test results, no irritating effects were seen for a dermal application of the tested substance.

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
other: experimental study on similar substance
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Toxnet reference - Jefca Evaluation
Qualifier:
no guideline available
Principles of method if other than guideline:
Human data on skin application
GLP compliance:
no
Species:
other: Human
Strain:
other: -
Preparation of test site:
not specified
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
25% aqueous solution
Duration of treatment / exposure:
The initial exposure to the compound was for 72 hours, and this was followed by a 24-hour application 10 to 14 days later.
Observation period:
-
Number of animals:
-
Details on study design:
200 human
Irritation parameter:
erythema score
Basis:
other: human
Time point:
14 d
Score:
0
Max. score:
5
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
None of the subjects exhibited compound induced irritation or sensitization
Interpretation of results:
GHS criteria not met
Conclusions:
The tested substance is not irritant to skin.
Executive summary:

None of the subjects exhibited compound induced irritation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
other: experimental study on similar substance
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Colipa report n. C174
Qualifier:
according to
Guideline:
other: Neutral Red Uptake assay (NRU) on human keratinocytes
Deviations:
not specified
Principles of method if other than guideline:
The NRU cytotoxicity assay procedure is a cell survival/viability chemosensitivity assay based on the ability of viable cells to incorporate and bind neutral red (NR), a supravital dye. NR is a weak cationic dye that readily penetrates cell membranes by non-ionic diffusion and accumulates intracellularly in lysosomes. Alterations of the cell surface or the sensitive lysosomal membrane lead to lysosomal fragility and other changes that gradually become irreversible. Such changes brought about by the action of xenobiotics result in a decreased uptake and binding of NR. It is thus possible to distinguish between viable, damaged, or dead cells, which is the basis of this assay.
In several studies for its ability to predict eye irritation potential as reflected by Draize scores. (Guidance Document on Using In VitroData to Estimate In Vivo Starting Doses for Acute Toxicity - ICCVAM)
GLP compliance:
not specified
Species:
human
Details on test animals or tissues and environmental conditions:
Human keratinocytes (HaCat).
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
Amount / concentration applied:
3.162 to 10000 µg/ml medium
Duration of treatment / exposure:
24 hours
Details on study design:
Monolayers of human keratinocytes (HaCat) were exposed in 96-well microtiter plates to various concentrations of Curry Red for 24 hours and cell viability was measured by neutral red uptake.
The concentration causing a 50 % reduction in neutral red uptake compared to the concurrent control (NRU-50) is determined. This figure, as a measure for
cytotoxicity of a test item in this cell culture, is compared to findings with known eye irritants under identical test conditions and allows a prediction of the eye irritation potential of a test item.
Irritation parameter:
in vitro irritation score
Value:
0
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
No NRU-50 value could be determined as the viability was still 71 % in the first and 69 % in the second assay after treatment with the highest test concentration of 10000 μg/ml medium.
Thus, the NRU-50 was > 10000 μg/ml.
The NRU-50 values obtained with the positive control SLS (12.5 and 15.6 μg/ml) were in the range of the historical control data of the laboratory and demonstrate the validity and sensitivity of the assay.
Interpretation of results:
GHS criteria not met
Conclusions:
Not eye irritant
Executive summary:

According to the classification system of the performing laboratory discriminating between non irritant, not-classified and severe, the tested substance is classified as non-irritant.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
other: experimental study on similar substance
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Colipa report num. C174
Qualifier:
according to
Guideline:
other: Hen's Egg Test - Chorioallantanoic membrane (HET-CAM)
Deviations:
not specified
Species:
chicken
Details on test animals or tissues and environmental conditions:
Commercially available fertilised white chicken eggs without micoplasms are used for the test.
Eggs are used on the 9th day of incubation, after having been controlled for embryo viability.
Weight: 50-60 g
Vehicle:
water
Controls:
yes
yes, concurrent positive control
Amount / concentration applied:
1 % aqueous solution
Duration of treatment / exposure:
The test item was rinsed off 30 seconds after application onto the Chorioallantanoic membrane (CAM).
Number of animals or in vitro replicates:
6 eggs per groups
Details on study design:
The eggs are opened near the air cell using a pair of surgical scissors. The section of the shell is carefully pared off to reveal the highly vascularised chorioallantoic membrane (CAM). 0.3 ml of test sample is applied on the CAM surface.
Irritation parameter:
other: Lysis
Run / experiment:
Time point: 0.5, 2 and 5 minutes
Value:
0
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation parameter:
other: Hemorrhage
Run / experiment:
Time point: 0.5, 2 and 5 minutes
Value:
0
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation parameter:
other: Coagulation
Run / experiment:
Time point: 0.5, 2 and 5 minutes
Value:
0
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The 1% aqueous solution did not cause any damaging effect on the CAM as the obtained evaluation resulted in score 0 for both independent experiments
Interpretation of results:
GHS criteria not met
Conclusions:
Not eye irritant
Executive summary:

The 1% aqueous solution did not cause any damaging effect on the CAM as the obtained evaluation resulted in score 0 for both independent experiments.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An vitro test following OECD 491 was performed on Acid Red 62 but the result was "not classificable" since no classification criteria were met.

The assessment for eye irritation was defined on available test data on similar substance.

Justification for classification or non-classification

Based on indication on the Regulation CE 1272/2008:

SKIN IRRITATION/CORROSION

A corrosive substance is a substance that produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least 1 tested animal after exposure up to 4 hour duration.

Three subcategories are provided within the corrosive category 1:

Subcategory 1A where responses are noted following up to 3 minutes exposure and up to 1 hour observation;

Subcategory 1B where responses are described following exposure between 3 minutes and 1 hour and observations up to 14 days;

Subcategory 1C where responses occur after exposures between 1 hour and 4 hours and observations up to 14 days

To classify a substance as irritant, the major criterion is that at least 2 of 3 tested animals have a mean score of ≥ 2,3 - ≤ 4,0.

Category 2:

- Mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from grading at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

- Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

- In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

The substance is not classified as skin irritant because in the performed tests it doesn't meet the classification criteria of the CLP regulation n. 1272/2008.

 

EYE IRRITATION

Serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance to the anterior surface of the eye, which is not fully reversible within 21 days of application.

Eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

Irreversible effects on the eye (Category 1):

If, when applied to the eye of an animal, a substance produces:

- at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/ or

- at least in 2 of 3 tested animals, a positive response of corneal opacity ≥ 3 and/or iritis > 1,5 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

These observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, discoloration of the cornea by a dye substance, adhesion, pannus, and interference with the function of the iris or other effects that impair sight. In this context, persistent lesions are considered those which are not fully reversible within an observation period of normally 21 days. Substances are also classified in Category 1 if they fulfil the criteria of corneal opacity ≥ 3 or iritis > 1,5 detected in a Draize eye test with rabbits, recognising that such severe lesions usually do not reverse within a 21-day observation period.

The substance does not meet the requirements to be classified in Category 1.

Irritating to eyes (Category 2)

when applied to the eye of an animal, a substance produces:

- at least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 1 and/or iritis ≥ 1, and/or conjunctival redness ≥ 2 and/or conjunctival oedema (chemosis) ≥ 2

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

The substance does not meet the requirements to be classified in Category 2.

Based on the available tests, the substance should be considered as not eye irritant.