Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2004-01-13 to 2004-02-03
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study, reliable with restrictions. 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 CaCO3.MgO. When administered to the skin for testing irritating properties (moistened with water, according to the test guideline EC B.4), CaCO3.MgO dissociates to a very limited extent into calcium-, magnesium-, carbonate-, and hydroxyl ions. 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 effect is due to a pH shift caused by the released hydroxyl ions. Magnesium and calcium ions are not associated with skin irritation. Also the carbonate is devoid of any irritation potency. Therefore a 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 skin irritation. Local effects due to calcined dolomite thus will be less severe than those arising from Ca(OH)2 or CaO. The read-across approach hence constitutes a worst case. In view of the fact that both calcium hydroxide/oxide and calcined dolomite 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 8.1 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:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
, adopted 2002-04-24
Deviations:
yes
Remarks:
, see "rationale for reliability"
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2003-06-04

Test material

Constituent 1
Reference substance name:
Calcium dihydroxide
EC Number:
215-137-3
EC Name:
Calcium dihydroxide
Cas Number:
1305-62-0
IUPAC Name:
calcium dihydroxide
Details on test material:
- Name of test material (as cited in study report): Calcium hydroxide (hydrated lime) in putty form (60 % H2O, 40 % Ca(OH)2) (from K. Raikos S.S., 6 Chris Smirnhs Str. PEFKI, Athens, Greece.
- Physical state: White paste (about 1300 kg/m³)
- Analytical purity: Ca(OH)2 +Mg(OH)2 ≥ 97 %
- Batch No.: Sample from the production of 10/12/2003 (The test item was labelled with the Lab. No. 02407 for this study.)
- Storage condition of test material: Room temperature
No further information on the test material was stated.

Test animals

Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: DIMED Schönwalde GmbH, 16352 Schönwalde
- Age at study initiation: approx. 11 to 17 months
- Weight at study initiation: 2.6-2.9 kg b.w.
- Housing: The rabbits were caged individually in PPO cages (floor area: 2576 cm²) with perforated floor.
- Diet (ad libitum): A pelleted complete rabbit diet "Alromin 2123" from Altromin, D-32791 Lage, Lippe.
- Water (ad libitum): Domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C +/- 3 °C
- Relative humidity: 55 % +/- 15 %
- Air changes: 10 times/hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test item
No further information on the test item was stated.
Duration of treatment / exposure:
Initial test (one rabbit): 3 minutes, 1hour and 4 hours
Confirmatory test (2 rabbits): 4 hours
Observation period:
Immediatly and 1 h, 24 h, 48 h, 72 h as well as on day 7 and 14 after termination of exposure
Number of animals:
3 rabbits
Details on study design:
Initial test:
On the experimental day one rabbit was physically restrained on a test table and its back was divided into six test fields. The left side of the body served as the test area for the test item. The test item was applied to a 16-layer gauze patch (2.5 X 2.5 cm), the patch was placed on the appropriate anterior test field and secured with adhesive Gothaplast tape (2.5 cm). After an exposure time of 3 min, the first patch was removed. Since no corrosive effects were observed a second patch with the test item was applied on the median test field of the rabbit back. In order to improve the patch securing the trunk of the animal was additionally wound with 5 cm wide adhesive Gothaplast tape. After 1 h the second patch was removed. Also, after 1 h no corrosive effects were observed so that the exposure time could be extended to 4 hours. The test item was applied on a third patch and put on the posterior test field of the animal. Adhesive Gothaplast tape (2.5 cm X 5 cm wide) served again as securing. After a 4-hour exposure time the third patch was removed.
Since the animal did not show any corrosive effect within a seven day observation period it was decided to carry out a confirmatory test with two additional animals.
Confirmatory test:
Likewise for the confirmatory test the animals were physically restrained on a test table and the back of each rabbit was divided in four test fields. Always the anterior left field was selected as the test area for the test item.
The test item was applied on a 16-layer gauze patch (2.5 cm X 2.5 cm) and the patch was placed on the appropriate test field. The gauze patch was secured with adhesive Gothsplast tape (2.5 cm wide) and fixed with Gothaplast tape (5 cm wide) loosely wound round the trunk of the animals.
TEST SITE
- Area of exposure: The day before the treatment the rabbits were weighed and the skin area on the back was clipped as closely as possible with an electric clipper.

REMOVAL OF TEST SUBSTANCE
- Washing: The treated skin was cleaned with mild soap and lukewarm water
- Time after start of exposure: Immediately

SCORING SYSTEM: Draize scoring system
No further information on the study design was stated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
2
Remarks on result:
other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48, and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
2
Remarks on result:
other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Remarks on result:
other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.
Irritant / corrosive response data:
After a maximum 4-hour exposure of calcium hydroxide (hydrated lime) in putty form (60 % H2O, 40 % Ca(OH)2) to the skin of the three test animals (Nos. 2692, 2632 and 2616) no skin corrosion but the following symptoms of irritation were observed during the subsequent 14-day observation period.
The animal No. 2692 used in the initial test showed a very slight erythema on the middle (1 h exposure period) and posterior (4 h exposure period) left test field immediately after the application.
1 h after termination of exposure a well defined erythema was observed on the posterior (4 h exposure period) left test field of the animal No. 2692 used in the initial test. Animal No. 2616 showed very slight erythema on the anterior left test field, whereas no skin reaction was observed at the remaining animal No. 2632.
24 and 48 h after termination of exposure the animal No. 2692 used in the initial test showed a well defined erythema on the middle (1 h exposure period) and posterior (4 h exposure period) left test field. A well defined erythema and a very slight oedema were oberved on the anterior left test field of another animal No. 2632. The remaining animal No. 2616 showed no signs of skin irritation.
72 h after termination of exposure a very slight erythema was observed on the middle (1 h. exposure period) left test field of the animal No. 2692 used in the initial test and a well defined erythema on the posterior left test field. Another animal No. 2632 showed a well defined erythema and a very slight oedema on the anterior left test field, whereas no skin reactions were observed at the remaining animal No. 2616.
7 days after termination of exposure animal No. 2632 showed a well defined erythema on the anterior left test field. The animal No. 2692 used in the initial test was free of any skin reactions, whereas on day 6 a very slight erythema was still observed on the middle (1 h exposure period) and posterior (4 h exposure period) left test field. The remaining animal No. 2616 did not show any signs of skin irritation, too.
14 days after the termination of exposure animal No. 2632 was also free of any skin reactions.

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.