Dolomite (CaMg(CO3)2), calcined

Eye irritation

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:

1994-11-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline study, reliable with restrictions. - The stability was not stated. - According to the guideline, any effects other than ocular which were observed should be stated. It was not mentioned in this study if other than ocular effects were observed. According to Annexes VII and VIII, point 8.2.1 of Regulation No 1907/2006 information on eye irritation (in vitro or in vivo) of substances shall be provided. Column 2 of Annex VII states that in vitro tests for eye 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 CaCO3.MgO. When administered to the eye for testing irritating properties (according to the test guideline EC B.5), CaCO3.MgO dissociates to a very limited extent into calcium-, magnesium-, carbonate-, and hydroxyl ions (here in lachrymal fluid). Calcined dolomite is in fact only poorly soluble in water, and consequently the pH of a saturated solution is ≤ 10.6 (see section 4.8 of the technical dossier, O'Connor and Woolley, 2010). Tests on skin and eye irritation are available for calcium hydroxide and calcium oxide. According to the test results, these two substances fulfil the criteria for classification as “risk of serious damage to eyes” and “irritating to skin”. Both calcium hydroxide and calcium oxide dissociate into Ca2+ and OH– ions. The irritating/damaging effect is due to a pH shift caused by the released hydroxyl ions. Magnesium and calcium ions are not associated with skin or eye irritation; also the carbonate is devoid of any irritation potency. Therefore the pH-shift (weaker than that caused by CaO or Ca(OH)2, with a pH 12.3 to 12.4; Fox, 2010a; Fox, 2010b) is the primary effect of CaCO3.MgO involved in eye irritation. In view of the fact that both calcium hydroxide/oxide and CaCO3.MgO result in the same “breakdown products” (except the carbonate, which is basically inert) 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. Based on the above considerations, CaCO3.MgO 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 following the precautionary principle. In conclusion, since at least one of the criteria for adaptation of testing requirements specified by column 2 of Annexes VII and VIII, point 8.2 is fulfilled (risk of serious damage to eyes, 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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

, adopted 1987-02-24

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Calcium oxide

EC Number:

215-138-9

EC Name:

Calcium oxide

Cas Number:

1305-78-8

IUPAC Name:

oxocalcium

Details on test material:

- Name of test material (as cited in study report): Calcium oxide (from Laboratoire Central Balthazar et Cotte)
- Physical state: White powder
- Analytical purity: 95.55 %
- Batch No.: 3314
- Storage condition of test material: At ambient temperature
- pH: The pH of the product, at 10 % concentration in distilled water, measured at the International Toxicology centre, was 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: 2782 g
- Housing: The animal was housed in 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 form of granules "Rabbit maintenance, Reference 112 C" (UAR, 91360 Villemoisson-sur-Orge, France).
- Water (ad libitum): Drinking water, filtered through an F.G.Millipore membrane (0.22 micron) is distributed in bottles.
- Acclimation period: 5 days before the sart 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 (volume or weight with unit): The lower eyelid was delicately opened, and a single dose of 100 mg of calcium oxide was introduced in the conjunctival cul-de-sac of the left eye. 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 is recorded.

TOOL USED TO ASSESS SCORE: If it was necessary the cornea was examined with an ultra-violet lamp. In the case of doubt as to the presence of corneal opacity, the eye is subjected to UV examination (the areas of corneal impairment are distinguished by a very clear fluorescence).
No further information on study design was stated.

Results and discussion

In vivo

Results

Results 1

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.

Results 2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: one hour after administration

Score:

2

Max. score:

2

Remarks on result:

other: Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons.

Irritant / corrosive response data:

One hour after administration, very severe eye reactions were observed with a slight chemosis, a necrotised appearance of the conjunctiva, and total opacity of the cornea, showing a nacreous appearance. The iris was no longer visible. A purulent whitish substance was observed.
Given the seriousness of the eye lesions observed, the animal was put down for humane reasons, and the product was not tested on two other 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 oxide, 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.