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Administrative data

Description of key information

Calcium lactate is not irritating to the skin. Calcium gluconolactate, containing calcium lactate is not irritating to the eyes, similar as shown for the structurally related magnesium-S-lactate, thus indicating that calcium lactate is not irritating to the 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to OECD Guidelines.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Species and strain: New Zealand White rabbits
Source: S&K-LAP Kft.
2173 Kartal, Császár út 135, HUNGARY
Justification of strain: The New Zealand White albino rabbit is one of the standard strains used for acute irritation toxicity studies.
Animal health: Only animals in acceptable health condition were used for the test.
Number of animals: 3
Age of animals at treatment: ~13 weeks old
Sex: Male
Body weight range at the
beginning of the life phase: 3125-3459 g
at the end of the life phase: 3199-3539 g
Date of receipt: 27 December 2012
Acclimation time: 19 days
Animal identification: The animals were identified by engraved ear tags. The cages were marked with individual identity cards with information about study code, sex, cage number, dose group and individual animal number.


3.2.1. Husbandry


Number of animal room: 609
Lighting periods: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature range during
the study: 20 ± 3 °C
Relative humidity during
the study: 25- 54%
Housing/Enrichment: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
Ventilation: 15-20 air exchanges/hour

The temperature and relative humidity values were measured continuously. The measured range was checked at least daily during the acclimatisation and experimental phases.



3.2.2. Food and Feeding


Animals received UNI diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum. Animals were provided with the following batch:
➢ 0161 10 12, expiry date: 15 January 2013
➢ 0181 11 12, expiry date: 24 February 2013

The details of the diets used will be archived with the raw data and are not reported.


3.2.3. Water Supply


The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin of test animals provided control.
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
The test item was applied to an approximately 6 cm² area of intact skin as follows:
• A single layer of a fine medical gauze (open-weave with large holes) of approximately 5x5 cm was placed over the application area,
• The appropriate amount of test item was carefully spread over the application area (the gauze helped maintain the test item in place),
• Three more layers of gauze were placed over the test item,
• These gauze patches were kept in contact with the skin by a patch of clear plastic with a surrounding adhesive hypoallergenic plaster to ensure continued good contact between the moistened test item and the shaved skin.
• The entire trunks of the animals were wrapped with plastic wrap for 4 hours.
• Medical elastic tubing was placed over the plastic to keep it in place.

Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24
Score:
0
Max. score:
0
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48
Score:
0
Max. score:
0
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72
Score:
0
Max. score:
0
Other effects:
None
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Not irritating
Executive summary:

Not irritating

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted according to GLP standards and OECD guideline 405: acute eye irritation/corrosion ( as valid in 1988). The tested product is calcium gluconolactate, i.e.a calcium salt of lactic acid and gluconic acid. Thus, while the test substance is not pure calcium(di)lactate, it contains both the calcium and the lactate components and hence is expected to provide adequate information for assessing possible eye irritating effects of calciumlactate.
Principles of method if other than guideline:
In vivo eye irritation test according to OECD guideline 405: acute eye irritation/corrosion ( as valid in 1988)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals, obtained from the Broekman Institute Someren, the Netherlands, weighing about 3 kg were acclimitized for at least 5 days prior to experimentation. Animals were individually housed in an air conditioned room (19-20 degrees of Celcius temperature and 50-75% relative humidity) with an artificial 12 hours light/ 12 hours dark cycle and received a standard diet (Hope Farms) and tap water ad libitum. Before administration of the test substanceboth eyes of all animals were inspected and found to be normal.
Controls:
not required
Duration of treatment / exposure:
Portions of powder (60 mg) were instilled in the conjunctival sac using a spatula. The lids were held gently for 2 seconds and released after that.
Observation period (in vivo):
After installation of the test-substance, animals were transferred to their cages, the animals were observed and any abnormalities recorded. Examination of the eyes was conducted at 1, 24, 48, 72 hours and at 7 days after test-substance application.
Number of animals or in vitro replicates:
A total of 3 rabbits were tested.
Details on study design:
The standard scoring system which is still applied in the latest (currently October 2012) version of OECD guideline 405: acute eye irritation/corrosion consisted of scoring lesions regarding cornea (opacity; ranked on a 0-4 scale), iris (amongst others reaction to light, swelling, hemorrhage; ranked on a 0-2 scale) conjunctiva redness and vascular structure (ranked on a 0-3 scale) and conjunctiva chemosis (ranked on a 0-4 scale) . Examination and scoring of the eyes was conducted at 1, 24, 48, 72 hours and at 7 days after test-substance application. In addition, after the examination and scoring on day 1, a 2% fluorescein solution in water (buffered at pH=7) was applied both to the eye that had received the substance and the control eye in order to examine potential corneal injury.
Irritant / corrosive response data:
The scores for eye irritation/corrosion are given in table 1. As can be seen, calcium gluconolactate only resulted in slight conjunctival chemosis 1 hour after substance application, which was no longer observed 24 hours or later after substance application. In addition, slight conjunctival redness was observed in all three animals at 1 hour after substance administration, which was still present after 24 hours in 2/3 animals and even up to 72 hours in 1/3 animals. In none of the animals, effects on the iris or cornea were observed . Finally, treatment of the eyes with flluorescein did not reveal corneal epithelila damage.
Other effects:
No signs of systemic toxicity were observed.

Table 1:  Eye irritation scores of calcium gluconolactate based on assessment and criteria of the OECD guideline protocol 405 (updated version of Februay 24, 1987 being valid at the time of the study) for testing chemicals regarding acute eye irritation/corrosion 

Scored itemand animal number Observation time (h after 60 mg of solid test substance application) 
Cornea  1h 24h 48h 72h 7 days mean of 24, 48 and 72 h
Rabbit 2888 0 0 0 0 0 0
Rabbit 2989 0 0 0 0 0 0
Rabbit 3236 0 0 0 0 0 0
Iris  1h 24h 48h 72h 7 days mean of 24, 48 and 72h
Rabbit 2888 0 0 0 0 0 0
Rabbit 2989 0 0 0 0 0 0
Rabbit 3236 0 0 0 0 0 0
Conjunctivae redness  1h 24h 48h 72h 7 days   mean of 24,48 and 72h 
Rabbit 2888 1 1 0 0 0 0,33
Rabbit 2989 1 1 1 1 0 1,00
Rabbit 3236 1 0 0 0 0 0
Conjunctivae chemosis  1h 24h 48h 72h 7 days mean of 24, 48 and 72h 
Rabbit 2888 1 0 0 0 0 0
Rabbit 2989 1 0 0 0 0 0
Rabbit 3236 1 0 0 0 0 0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Using the OECD protocol 405 and the therein described scoring system and applying the obtained mean values for the 24, 48 and 72 hour scores to the classification criteria for eye irritants using the EC1272/2008 guidelines and the corresponding November 2012 guidance for applying CLP criteria, calcium gluconolactate should be classified "non irritating". Calcium gluconolactate is a mixture of the calcium salts of lactate and gluconate, thus as such it is not identical to calcium (di) lactate, but does contain it. Therefore, it is highly likely that the results obtained for calcium gluconolactate that are based on state of the art standardized protocols, do also apply for calcium(di)lactate. Consequently, calcium(di)lactate should be classified as non irritant. Further data (albeit indirect, since based on read across) supporting this are given in "Eye irritation.002"
Executive summary:

In an in vivo eye irritation test according to the OECD protocol 405 it was shown that calciumgluconolactate is non irritant to the eyes., EC1272/2008 guidelines and the corresponding November 2012 guidance for applying CLP criteria.

Since calcium gluconolactate contains both the calcium cation and the lactate anion (next to the gluconate anion) it is highly likely that it has similar intrinsic eye irritating characteristics than calcium(di)lactate itself. Consequently, calcium(di)lactate should be classified as a non-irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The conclusions are drawn on a GLP, OECD Guideline study for skin irritation, showing that calcium lactate is not irritating to the skin of New Zealand rabbit, when tested under the specific conditions. Concerning eye irritation of calcium lactate: an OECD guideline study on a mixture containing calcium lacate and -gluconate (calcium gluconolactate) and a OECD guidlinestudy on magnesium-s-lacate (being structurally related to calcium lactate) showed that calcium gluconolactate nor magnesium-S-lactate is irritating to the eyes. Thus, from this it can be deduced that calcium lactate is not irritating to the eyes.


Justification for selection of skin irritation / corrosion endpoint:
A GLP, OECD Guideline study is available that examines the skin irritation potential of calcium lactate and fully addresses this endpoint. Based on the results of the study the test material is not irritating to the skin of New Zealand rabbit, when tested under the specific conditions.

Justification for selection of eye irritation endpoint:
This conclusion is based on OECD guideline study (Eye irritation.001) for calcium gluconolacate (ie a mixture of calcium gluconate and calcium lactate) showing that calcium gluconolacate is non-irritant to the eye. From this it is derived that calcium lacate is non-irritant to the eye, a conclusion which is further supported by read across with a OECD guideline study on magnesium-S-lacate (Eye irritation.002) , that proved to be non-irritant as well.

Justification for classification or non-classification

From the above it follows that calcium lactate is highly likely not to be irritating to the skin or the eye. Hence, no classification is required for these two toxicological endpoints according to the EC1272/2008 guidelines and guidance on the application of CLP of November 2012.

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