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Eye irritation

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Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988

Materials and methods

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

Test material

Constituent 1
Reference substance name:
calcium gluconolactate
IUPAC Name:
calcium gluconolactate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
60 mg of calciumgluconolactate (95% pure, the other 5 % being water) in powder form was applied, corresponding to a volume of approximately 0,1 ml

Test animals / tissue source

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.

Test system

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.

Results and discussion

In vivo

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.

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