Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1994-12-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Minor deviations with no effect on the results: - Stability was not given - Animal weights at conclusion of test were missing According to Annexes VII and VIII, point 8.1.1 of Regulation No 1907/2006 information on skin irritation (in vitro or in vivo) of substances shall be provided. Column 2 of Annex VII states that in vitro tests for skin corrosion or skin irritation need not be conducted if the criteria for classification as irritating to the eyes are met. In addition, Annex XI specifies rules for adaptation of the standard testing requirements. Point 1.5 of Annex XI permits read-across from substances showing similarities based on, amongst others, common functional groups. This read-across concept is applicable to "Reaction mass of limestone and dicalcium silicate". When administered to the skin for testing irritating properties (moistened with water, according to the test guideline EC B.4), calcium hydroxide, constituent of "Reaction mass of limestone and dicalcium silicate”, dissociates into calcium- and hydroxyl ions in aqueous solutions, whereas calcium carbonate and silicate remain largely undissolved and are therefore of limited toxicological relevance. Tests on skin and eye irritation are available for calcium hydroxide. According to the test results, calcium hydroxide fulfils the criteria for classification as “risk of serious damage to eyes” and “irritating to skin”. Calcium hydroxide dissociates into Ca2+ and OH– ions. The irritating/damaging effect is due to a pH shift caused by the released hydroxyl ions. Calcium ions are not associated with skin irritation; therefore the pH-shift is the primary effect of "Reaction mass of limestone and dicalcium silicate" involved in skin irritation. In view of the fact that both calcium hydroxide and "Reaction mass of limestone and dicalcium silicate"result in the same “breakdown products” when administered in the appropriate test system, they can be considered as analogue substances, fulfilling criteria (1) and (2) of Annex XI, point 1.5. In addition, the pH of a saturated solution of "Reaction mass of limestone and dicalcium silicate" has been determined at 12.61, whereas Ca(OH)2 creates a pH value of 12.4 (Fox, 2010b). Therefore, local effects due to "Reaction mass of limestone and dicalcium silicate"will be approximately equivalent to those arising from Ca(OH)2. Based on the above considerations, "Reaction mass of limestone and dicalcium silicate"is voluntarily proposed to be classified as R38 (irritating to skin) and R41 (risk of serious damage to eye) by read-across, which is therefore a conservative approach. In conclusion, since at least one of the criteria for adaptation of testing requirements specified by column 2 of Annexes VII and VIII, point 8.1 is fulfilled (risk of serious damage to eyes, irritating to skin, by read-across), any further testing is considered to be scientifically unjustified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Calcium hydroxide (from Laboratoire Central Balthazar et Cotte)
- Physical state: White powder
- Batch No.: 3542
- Storage condition of test material: At ambient temperature
- pH: The pH of the product, at 10 % concnetration in distilled water, measured at the International Toxicology Centre, was about 9.
No further information on the test material was stated.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Weight at study initiation: 2708 g
- Housing: polystyrene cage (35 X 55 X 32 cm or 48.2 X 58 X 36.5 cm) equipped with a trough and bottle.
- Diet (ad libitum): Food in the form of granules " Rabbit maintenance, Reference 112 C" (UAR, 91360 Villemoisson-sur-Orge, France).
- Water (ad libitum): Drinking water
- Acclimation period: 5 days before the start of the study
ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 3 °C
- Humidity: 30 to 70 %
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animal was stated.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: The lower eyelid was delicately opened, and a single dose of 100 mg of the product as such was introduced in the conjuctival cul-de-sac of the left eye of the animal. The lower and
upper lids were maintained in contact for a second to prevent any loss of product. The right eye was administered no product and served as control.
No further information on amount/concentration applied was stated.
Observation period (in vivo):
The eyes were examined 1 hour after the administration of the product.
Number of animals or in vitro replicates:
one male rabbit
Details on study design:
REMOVAL OF TEST SUBSTANCE
The eyes were not rinsed after the administration of the product.
SCORING SYSTEM: Draize scoring system
All other damage observed was recorded.
TOOL USED TO ASSESS SCORE: If necessary the cornea was examined with an ultra-violet lamp. In the case of doubt as to the presence of corneal opacity, the eye was subjected to UV examination (the
areas of corneal impairment are distinguished by a very clear fluorescence).
No further information on the study design was stated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 1 hour after administration
Score:
4
Max. score:
4
Remarks on result:
other: Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons, and the product was not tested on the other 2 rabbits.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1 hour after administration
Score:
3
Max. score:
3
Remarks on result:
other: Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons, and the product was not tested on the other 2 rabbits.
Irritant / corrosive response data:
Very severe eye reactions were observed 1 hour after the treatment, with pronounced chemosis (score:3), necrotised appearance of the conjunctiva, whitish watering and total opacity of the cornea, showing nacreous appearance. The iris was no longer visible.
Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons, and the product was not tested on the other 2 rabbits.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study described in this report and applying read-across from calcium hydroxide, calcined dolomite (CaCO3.MgO) is voluntarily proposed to be classified as R38 (irritating to skin) and R41 (risk of serious damage to eye) according to Directive 67/548/EEC and subsequent regulations by read-across. This is a conservative approach following the precautionary principle, in view of the weaker pH effect of calcined dolomite.