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Administrative data

Description of key information

Skin corrosion: not corrosive (OECD 435, GLP)
Skin irritation: not irritating (OECD 404, GLP)
Eye irritation: corrosive/severe irritant to the eyes (OECD 437, GLP)

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:
2015-09-23 to 2015-10-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 2002-04-24
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2015-05-14
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Manfred Bauer Kaninchen, Lohe 7/1, 74632 Neuenstein, Germany
- Age at dosing: approx. 3 - 4 months
- Weight at dosing: 3.0 to 3.2 kg
- Housing: individually housed in cages measuring 380 mm x 425 mm x 600 mm (manufacturer: Dipl. Ing. W. EHRET GmbH, 16352 Schönwalde, Germany); during the exposure the animals were kept in comfortable restrainers.
- Diet (ad libitum before and after the exposure period): commercial diet, ssniff® K-H V2333 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: at least 20 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 20°C ± 3°C (maximum range)
- Relative humidity: 30% - 70% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg/patch
The test item was mortared and moistened with the vehicle.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.2 mL water
Duration of treatment / exposure:
4 hours
Observation period:
directly after removal of the patch, 60 minutes, 24, 48 and 72 hours after patch removal
Number of animals:
3 female rabbits
Details on study design:
TEST SITE
- Area of exposure/Type of wrap if used: approximately 24 hours before the test, the fur was removed by closely clipping the dorsal area of the trunk of the animals.
The test item was applied to the test site (area: approx. 6 cm²) and then covered with a gauze patch. The patch was loosely held in contact with the skin by means of a suitable semi-occlusive dressing for the duration of the exposure period. The surrounding untreated skin served as a control.

INITIAL TEST AND CONFIRMATORY TEST
- Initial test using one animal:
Three test patches were applied sequentially to the animal. The first patch was removed after three minutes. As no serious skin reaction was observed, a second patch was applied at a different site and removed after one hour. No skin reactions were observed, neither. So a third patch was applied and removed after 4 hours.
- Confirmatory test:
As no skin reactions were observed, the test was completed using two additional animals, each with one patch only, for an exposure period of 4 hours.
SCORING SYSTEM: according to the Draize scale
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
None of the three rabbits exposed for 4 hours to 500 mg strontium neodecanoate/patch (semi-occlusive conditions) revealed any skin reaction.
Other effects:
There were no systemic intolerance reactions.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Strontium neodecanoate is not irritating to the skin.
According to the EC-Commission directive 67/548/EEC, strontium neodecanoate is not classified as irritating to the skin.
According to the EC-Regulation 1272/2008, strontium neodecanoate is not classified as irritating to the skin.
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:
2015-04-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Version / remarks:
adopted 2013-07-26
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Bovine Corneal Opacity and Permeability (BCOP) Assay, SOP of Microbiological Associates Ltd., UK, Procedure Details, April 1997
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2013-04-11
Details on test animals or tissues and environmental conditions:
Not applicable - Since this is an in vitro study there is no information on test animals.
Vehicle:
physiological saline
Amount / concentration applied:
TEST MATERIAL
- Concentration: test item was tested as a 20% suspension (w/v) in saline. Due to insoluble clumps of the test item, therefore one clump of the test item in 0.75 mL of the prepared coarse suspension was distributed to each cornea. Thereby it was taken care of that the corneae were evenly covered with the test item.
Duration of treatment / exposure:
240 minutes
Observation period (in vivo):
not applicable
Number of animals or in vitro replicates:
not applicable
Details on study design:
COLLECTION OF BOVINE EYES
- isolated bovine eyes of at least 9 month old donor cattle were collected from the abattoir and were transported in Hank's buffered salt solution (HBSS) supplemented with streptomycin / penicillin at ambient temperature.

PREPARATION OF CORNEAE
- all eyes were carefully examined macroscopically for defects.
- the cornea was carefully removed from the eye.
- each cornea was mounted in a specially designed cornea holder according to the description given in OEDC guideline 437, that consists of anterior and posterior compartments, which interface with the epithelial and endothelial sides of the cornea, respectively. Both compartments of the holder were filled with incubation medium.
- for equilibration, the corneae in the holder were incubated in a vertical position for one hour at 32 ± 1 °C in a water-bath.
- at the end of the incubation period, the basal opacity was determined (t0) of all cornea.
- each corneae with a value of the basal opacity > 7 was discarded.

EXPOSURE OF THE CORNEAE TO THE TEST GROUPS
- the anterior compartment received the test item suspension or negative control (saline) or positive control (10% (w/v) benzalkonium chloride in 0.9% (w/v) NaCl (saline)) at a volume of 0.75 mL each on the surface of the corneae.
- the corneae were incubated in a horizontal position at 32 ± 1 °C in the water-bath (incubation time: 240 minutes).
- the test item, positive control and negatice control were tested in triplicate.
- the test item or control items were rinsed off with saline
- incubation medium was added into the anterior compartment and opacity was measured (t240)
- permeability of the corneae was determined.

PERMEABILITY MEASUREMENT
- after the final opacity measurement, the incubation medium was removed from the anterior compartment and replaced by 0.5% (w/v) sodium fluorescein solution in HBSS.
- corneae were incubated in a horizontal position for 90 ± 10 minutes in a water-bath at 32 ± 1 °C.
- incubation medium from the posterior compartment was removed, well mixed and the optical density at 490 nm was determined with a spectrophotometer. The absorbance values were determined using the software SoftMax Pro Enterprise, version 4.7.1.

EVALUATION OF RESULTS
- Opacity: the change of opacity value of each treated cornea or positive and negative control corneae is calculated by subtracting the initial basal opacity from the post treatment opacity reading (t240 – t0), for each individual cornea.
The average change in opacity of the negative control corneae is calculated and this value is subtracted from the change in opacity of each treated cornea or positive control to obtain a corrected opacity.
- Permeability: the corrected OD490 value of each cornea treated with positive control and test item is calculated by subtracting the average negative control cornea value from the original permeability value for each cornea.

IN VITRO IRRITATION SCORE CALCULATION
The following formula was used to determine the in vitro irritation score (IVIS) of the negative control:
In vitro Irritation Score = opacity value + (15 x OD490 value)
The following formula was used to determine the in vitro irritation score of the positive control and the test item:
In vitro Irritation Score = (opacity value – opacity value mean negative control) + (15 x corrected OD490 value)
The mean IVIS value of each treated group was calculated from the IVIS values.
Depending on the score obtained, the test item was classified into the following category according to OECD guideline 437 (table 1 in the field "Any other information on materials and methods incl. tables" below)

CRITERIA FOR DETERMINATION OF A VALID TEST
The test was acceptable if
- the positive control gives an IVIS that falls within two standard deviations of the current historical mean (updated every three months), and if
- the negative control responses result in opacity and permeability values that are less than the established upper limits for background opacity and permeability values for bovine corneae treated with the respective negative control.
Irritation parameter:
in vitro irritation score
Run / experiment:
Time point: 240 min.
Value:
166.9
Other effects / acceptance of results:
Relative to the negative control, the test item strontium neodecanoate caused an increase of the corneal opacity and permeability. The calculated mean IVIS was 166.90 (threshold for serious eye damage: IVIS ≥ 55). According to OECD 437 the test item is classified as serious eye damaging.

Table 1: Results after 240 minutes incubation time

Test group

Opacity value = Difference (t240 – t0) of opacity

Permeability at 490 nm (OD490)

In vitro irritancy score

Mean in vitro irritancy score

 

 

Mean

 

Mean

 

 

Negative control

0

 

0.33

0.075

 

0.091

1.13

 

1.69

1

0.119

2.79

0

0.078

1.17

Positive control

127.67*

0.067*

128.68

 

124.79

127.67*

0.055*

128.50

114.67*

0.168*

117.19

Strontium neodecanoate

149.67*

1.622*

174.00

 

166.90

131.67*

1.680*

156.87

144.67*

1.677*

169.83

* corrected values

-With the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed (mean IVIS = 1.69).

- The positive control (10% (w/v) Benzalkonium chloride in saline) showed clear opacity of the corneae (mean IVIS =124.792).

Table 2: Historical data

 

Positive control

Negative control

Mean IVIS

176.58

1.71

Standard deviation

41.85

0.76

Range of IVIS

62.60 - 292.29

0.00 – 3.00

Values of 206 studies with solid test items performed from February 2007 until December 2014 based on 0.5% sodium fluorescein solution in HBSS (w/v) and sodium fluorescein solution of 200 µL per well

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, according to the current study and under the experimental conditions reported, strontium neodecanoate is serious eye damaging.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin corrosion/irritation

A reliable in vitro study described by Roth (2015)(OECD 435) is considered to be reliable without restrictions. The substance was determined not to be corrosive to the skin.

Furthermore, one reliable in vivo study described by Hansen (2015)(OECD 404) is considered to be reliable without restrictions. The substance was determined not to be irritating to the skin.

Eye irritation:

One reliable in vitro eye irritation described by Roth (2015)(OECD 437) is considered to be reliable without restrictions.

The test item is corrosive/severe irritating to the eyes.

Justification for classification or non-classification

Skin corrosion:

The test item does not possess a skin corrosive potential and does not require classification as corrosive to skin according to Regulation (EC) No 1272/2008 and subsequent regulations.

Skin irritation:

The test item does not possess a skin irritation potential and does not require classification as skin irritant according to Regulation (EC) No 1272/2008 and its subsequent regulations.

Eye irritation:

The test item does require classification for serious eye damage according to OECD 437 (2013) and the test item does cause serious eye damage Category 1 (H318: causes serious eye damage) according to the Regulation (EC) No 1272/2008 and subsequent regulations.

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