Registration Dossier

Administrative data

Description of key information

The irritating behaviour of the substance on skin and eyes has been determined in adequate studies in vivo and in vitro by application of the substance into the skin and into the eye. No studies are available for respiratory irritation.

For skin irritation/corrosion there is one key study, performed following test methods similar to OECD 404 (pre-GLP and non-GLP).

The key study is a recent study of Alvarez i Genoher N (2002) performed with the substance CAS 1195028 -55 -7. This substance didn't show irritating properties when applied to skin of rabbits. The result of this key study supports the classification as non irritant.The study has the highest reliability, it is a recent one, and the sample is in powder form from the reaction mass with a higher degree of purity

In a supporting study from Thomann P (1973) the test material used for testing was CAS 1325-54-8 / EC 215-397-8, a substance of identical structure of CAS1195028-55-7 in respect to the anionic structure, but with Na+ cations instead of a mixture of Na+ and Li+. No classification is warranted for CAS 1325 -54 -8 with regard to skin irritation according to CLP Regulation.

For eye irritation there are 2 studies in vitro and 1 study in vivo available.

The three tests have been done on the substance in different compositions. The first one done by Alvarez G (2003), was an in vivo study following a guideline similar to OECD 405, and was not GLP compliant. The test material used was the substance in a liquid formulation and the result of the test showed effects of the composition as eye irritant. The second one done by Bradshaw (2013), an in vitro Rabbit Enucleated Eye Test GLP compliant, was performed on a solid powder form of low purity. The result revealed too the potential of the substance to cause severe ocular irritancy in vivo. The most recent test done by Pooles A (2015) is also a Rabbit Enucleated Eye Test GLP compliant

that has been performed on the substance with CAS 1195025-55-7, pure concentrated solid in powder form. The results of this test showed no potential of the substance to cause ocular irritancy in vivo. The study of Pooles A (2015) is the study which has the highest reliability, it is a GLP recent one. The tested sample is the one with the highest purity compared to the former compositions tested and it has been chosen as the key study for this endpoint.

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
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
similar to OECD 404, non-GLP
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Authorized distributor
- Housing: stainless individual cage
- Diet (e.g. ad libitum): 150g/day of special diet for experimental rabbits
- Water (e.g. ad libitum): automatic ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +- 2
- Humidity (%): 55 +- 25
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Lot/batch no. (if required): 2619427
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: 6 square centimeter

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 4 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0

Erythema and Eschar Formation

No erythema ......................................................................................................................... 0

Very slight erythema (barely perceptible) ................................................................................ 1

Well defined erythema ............................................................................................................ 2

Moderate to severe erythema ................................................................................................. 3

Severe erythema (beet redness) to slight eschar formation (injuries in depth) ............................ 4

Total possible erythema score 4

Edema formation

No edema .............................................................................................................................. 0

Very slight edema (barely perceptible) .....................................................................................1

Slight edema (edges of area well defined by definite raising) ..................................................... 2

Moderate edema (raised appoximately 1mm) .......................................................................... 3

Severe edema (raised more than 1mm and extending beyond area of exposure) ....................... 4

Total possible edema score 4

Weight table

 Rabbit  Weight (g)
 N° 1  2462
 N° 2  2492
 N° 3  2567

Mean valours of Erithemas and Edemas observed in rabbits after 1, 24, 48 and 72 h of application

   Mean score of Erithema  Mean score of Edema
 Rabbit N° 1  0.67  0.00
 Rabbit N° 2  0.67  0.00
 Rabbit N° 3  0.67  0.00
All   0.67  0.00
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Any of the rabbits treated with the substance has showed an erythema scored or edema score >=2. According to the test conditions the tested substance is not classified as skin irritant.
Executive summary:

3 New Zealand white rabbit were dosed with 0.5g or 0.5ml of solid samples or liquid samples respectively of substance. After 4 hours of exposure period the test material was removed with water or appropiate solvent and after 1, 24, 48 and 72 hours the animals were observed.

The sample is considered not irritating due to neither acute erithemas nor edemas are not seen in the animals after the substance is applied.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
other: Rabbit enucleated eye test
Version / remarks:
ICCVAM, 2006 and 2009
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals were 12 to 20 weeks old. Rabbits that have previously been used in skin or eye irritation studies at the test facility may be used as eye donors. If the donor animals have been used in an eye irritation study, only the untreated eyes were used.
Vehicle:
physiological saline
Controls:
yes
Amount / concentration applied:
A volume of 0.1 mL of the test item, which was found to weigh approximately 91 mg
Duration of treatment / exposure:
After 10 seconds the test item was washed off the cornea using a minimum of 20 mL of saline solution (approximately 32 °C).
Immediately following washing of the corneal surface, the treated eye was returned to the superfusion chamber and the saline drip repositioned to irrigate the eye.
Number of animals or in vitro replicates:
3
Details on study design:
Assessment of corneal cloudiness was made pre-enucleation, post equilibration and approximately 60, 120, 180 and 240 minutes following treatment.
Measurements for corneal thickness were carried out pre-enucleation, post equilibration and approximately 60, 120, 180 and 240 minutes following treatment.
The condition of the corneal epithelium was assessed approximately 60, 120, 180 and 240 minutes following treatment.
The uptake of fluorescein by the corneal epithelium was assessed pre-enucleation, post equilibration and approximately 240 minutes following treatment

Irritation parameter:
cornea opacity score
Run / experiment:
1A
Value:
0
Irritation parameter:
cornea opacity score
Run / experiment:
3A
Value:
0
Irritation parameter:
cornea opacity score
Run / experiment:
5A
Value:
0
Irritation parameter:
fluorescein retention score
Run / experiment:
1A
Value:
0
Irritation parameter:
fluorescein retention score
Run / experiment:
3A
Value:
0
Irritation parameter:
fluorescein retention score
Run / experiment:
5A
Value:
0
Irritation parameter:
percent corneal swelling
Remarks:
% Mean corneal swelling 1 hour following treatment
Run / experiment:
mean of 3 test eyes
Value:
12.2
Irritation parameter:
percent corneal swelling
Remarks:
% Mean corneal swelling 2 hour following treatment
Run / experiment:
Mean of 3 test eyes
Value:
11.4
Irritation parameter:
percent corneal swelling
Remarks:
Mean corneal swelling 4 hours following treatment
Run / experiment:
mean of 3 test eyes
Value:
6.6
Irritation parameter:
percent corneal swelling
Remarks:
60 min
Run / experiment:
mean of 2 control eyes
Value:
7.2
Irritation parameter:
percent corneal swelling
Remarks:
120 min
Run / experiment:
mean of 2 control eyes
Value:
7.4
Irritation parameter:
percent corneal swelling
Remarks:
240 min
Run / experiment:
mean of 2 control eyes
Value:
5.3
Irritation parameter:
morphological effects
Remarks:
Condition of Corneal Epithelium
Run / experiment:
3 runs
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Following assessment of the data for all endpoints the test item was considered unlikely to have the potential to cause severe ocular irritancy in vivo.
Executive summary:

A study was performed to assess the ocular irritancy potential of the test item in the rabbit following application onto the cornea of the enucleated eye. The results of the study are believed to be of value in predicting the ocular irritation potential of the test item in man.

0.1 mL of the test item, which was found to weigh approximately 91 mg, was applied onto the cornea of each of three enucleated eyes which had been maintained at a temperature of 32 ±1.5 °C within the superfusion chamber. A further two enucleated eyes remained untreated for control purposes.

Maximal ocular irritation observations recorded for the test eyes were as follows: Corneal Opacity (score 0), Fluorescein Uptake (score 0), Corneal Swelling (60 mins 12.2% test eyes mean of 3 runs vs 7.2% control eyes mean of 2 runs, 120 mins 11.4% test eyes mean of 3 runs vs 7.4% control eyes mean of 2 runs, 240 min 6.6% test eyes mean of 3 runs vs 5.3% control eyes mean of 2 runs), condition of corneal Epithelium (normal).

Following assessment of the data for all endpoints the test item was considered unlikely to have the potential to cause severe ocular irritancy in vivo.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin irritation: 

The study of Alvarez G (2002) has been considered for classification purposes. The result of this study shows no irritation effects due to neither acute erithema nor edemas are seen in the animals after the substance has been applied to them. The values obtained lead to the conclusion that the substance doesn't fall into the range for classification of the substance as skin irritant according to CLP Regulation(EU Regulation 1272/2008).

Eye irritation:

The study of Pooles A (2015) has been considered for classification purposes. The results of the study report shows a nul potential for the substance to cause eye irritation, and therefore it is not classified as Eye Irritant.