Lime (chemical), hydraulic

Endpoint summary

Description of key information

Lime (chemical) hydraulic is considered to be irritating to skin and the respiratory system and entails a risk of serious damage to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-01-13 to 2004-02-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

, adopted 2002-04-24

Deviations:

yes

Remarks:

Stability was not given - Animal weights at conclusion of test were missing

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2003-06-04

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.

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:

Immediately 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.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no erythema observed

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

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.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Based on the results of the study described in this report and according to the Directive 67/548/EEC and subsequent regulations, calcium hydroxide (hydrated lime) in putty form (60 % H2O, 40 % Ca(OH)2), shall be classified as skin irritating but shall not be classified as corrosive.
Based on the results of the study described in this report and according to the EC Regulation No. 1272/2008 and subsequent regulations, calcium hydroxide (hydrated lime) in putty form (60 % H2O, 40 % Ca(OH)2), shall be classified as non-irritating.
CaH2MgO3 is voluntarily proposed to be classified as R38 (irritating to skin) and R41 (risk of serious damage to eye) by read-across, which is a conservative approach (pH effect).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2 June 2004 to 5 June 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: David Percival Ltd, Moston, Sandbach, Cheshire UK.
- Weight: 2.0 to 3.5 kg
- Age: 12 - 20 weeks old.
- Acclimation period: at least 5 days
- Housing: the animals were individually housed in suspended metal cages
Free access to mains drinking water and food (Certified Rabbit Diet code 5322) allowed throughout the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

0.5 g of test material moistened with 0.5 mL of distilled water

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after removal of the patches

Number of animals:

3 male animals

Details on study design:

TEST SITE
- Area of exposure: Dorsal/ flank - 2.5 cm x 2.5 cm area
- % coverage: No data
- Type of wrap if used: The cotton gauze patch was secured in position with a strip of adhesive tape and the trunk of each rabbit was then wrapped in an elasticated corset.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

other: Mean scores for all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Mean scores calculated according to the criteria described in Regulation (EC) No 1272/2008

Irritation parameter:

edema score

Basis:

other: Mean scores for all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Mean scores calculated according to the criteria described in Regulation (EC) No 1272/2008

Irritant / corrosive response data:

No evidence of skin irritation was noted during the study.

Other effects:

No data

Table 1: Individual Skin Reactions

Skin reaction	Observation Time	Individual scores – Rabbit Number and Sex			Total
		29 Male	30 Male	31 Male
Erytheme/Eschar Formation	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0	0 0 0 0	( 0 ) 0 ( 0 ) 0
Oedema Formation	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0	0 0 0 0	( 0 ) 0 ( 0 ) 0
Classification:                                          NON-IRRITANT

No evidence of skin irritation was noted during the study

Interpretation of results:

GHS criteria not met

Conclusions:

No evidence of skin irritation or corrosive effects were noted during the study. All the indivdual scores were 0; hence, the mean scores for 24, 48 and 72 hours for each animal were also 0. PCC is therefore non-irritating to rabbit skin and does not require classification according to the criteria described in Regulation (EC) No 1272/2008.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Common functional groups/mechanism of action.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target: Lime (chemical), hydraulic [CAS 85117-09-5; See section 1.2 for information on purity.
Source: calcium dihydroxide [CAS 1305-62-0; EC 215-137-3] (60 % H2O, 40 % Ca(OH)2) as a putty; analytical purity Ca(OH)2 +Mg(OH)2 ≥ 97 %

3. ANALOGUE APPROACH JUSTIFICATION
When administered to the skin for testing irritating properties (moistened with water, according to the test guideline EC B.4), the main constituent of lime (chemical) hydraulic, calcium hydroxide 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 lime (chemical) hydraulic involved in skin irritation. In view of the fact that both calcium hydroxide and lime (chemical) hydraulic 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 lime (chemical) hydraulic has been determined at 12.3 (see section 4.8, O'Connor and Woolley, 2010), whereas Ca(OH)2 creates a pH value of 12.4 (Fox, 2010b). Therefore, local effects due to lime (chemical) hydraulic will be approximately equivalent to those arising from Ca(OH)2.

4. DATA MATRIX
Source: No studies available
Target: Category 2 (irritant), based on pH effect.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no erythema observed

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-12-22

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline study, reliable with restrictions. - The purity and stability was not given in the test report. Minor deviation with no effect on the study results: - According to the guideline, any effects other than ocular which are 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 lime (chemical) hydraulic. When administered to the eye for testing irritating properties (according to the test guideline EC B.5), the main constituent of lime (chemical) hydraulic, calcium hydroxide dissociates into calcium- and hydroxyl ions in aqueous solutions (here in lachrymal fluid), 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 lime (chemical) hydraulic involved in eye irritation. In view of the fact that both calcium hydroxide and lime (chemical) hydraulic 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 lime (chemical) hydraulic has been determined at 12.3 (see section 4.8, O'Connor and Woolley, 2010), whereas Ca(OH)2 creates a pH value of 12.4 (Fox, 2010b). Therefore, local effects due to lime (chemical) hydraulic will be approximately equivalent to those arising from Ca(OH)2. Based on the above considerations, lime (chemical) hydraulic 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 8.2 is fulfilled (risk of serious damage to eyes, irritating to skin, by read-across), any further testing is considered to be scientifically unjustified.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

, adopted 1987-02-24

Deviations:

yes

Remarks:

purity and stability not reported. It was not mentioned in this study if other than ocular effects were observed.

GLP compliance:

yes

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.

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.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hour after administration

Score:

4

Max. score:

4

Reversibility:

not specified

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:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons after the 1 hour observation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour after administration

Score:

3

Max. score:

4

Reversibility:

not specified

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:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons after the 1 hour observation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour after administration

Max. score:

2

Reversibility:

not specified

Remarks on result:

not determinable

Remarks:

iris not visible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons after the 1 hour observation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons after the 1 hour observation

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.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

14 June 2004 to 24 June 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: David Percival Ltd, Moston, Sandbach, Cheshire UK.
- Weight: 2.0 to 3.5 kg
- Age: 12 - 20 weeks old.
- Acclimation period: at least 5 days
- Housing: the animals were individually housed in suspended metal cages
Free access to mains drinking water and food (Certified Rabbit Diet code 5322) allowed throughout the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Vehicle:

unchanged (no vehicle)

Controls:

other: Left eye served as control

Amount / concentration applied:

0.1 mL of the test material (~61 mg)

Duration of treatment / exposure:

Animals were exposed to the test material for up to 72 hours.

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3 male animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
Not specified


SCORING SYSTEM: Assessment of ocular damage/ irritation was made according to Draize. Ocular irritancy potential of the test material was determined using a modified version of the system described by Kay and Calandra.


TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

other: Mean scores for all animals

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Remarks on result:

other: Mean scores calculated according to the criteria described in Regulation (EC) No 1272/2008

Irritation parameter:

iris score

Basis:

other: Mean scores for all animals

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Remarks on result:

other: Mean scores calculated according to the criteria described in Regulation (EC) No 1272/2008

Irritation parameter:

conjunctivae score

Basis:

other: Mean scores for all animals

Time point:

24/48/72 h

Score:

0.67

Reversibility:

fully reversible

Remarks on result:

other: Mean scores calculated according to the criteria described in Regulation (EC) No 1272/2008

Irritation parameter:

chemosis score

Basis:

other: Mean scores for all animals

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Remarks on result:

other: Mean scores calculated according to the criteria described in Regulation (EC) No 1272/2008

Irritant / corrosive response data:

No corneal effects were noted during the study.
Iridial inflammation was noted in all treated eyes one hour after treatment.
Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48 hour observations.
All treated eyes appeared normal at the 72 hour observation.

Other effects:

The initial pain reaction was grade 2 (rabbit blinks and tries to open eye but reflex closes it, slight initial pain).

Table 1: Individual scores and individual total scores for ocular irritation

Rabbit number and sex	83 Male (IPR = 2)				26 Male (IPR = 2)				27 Male (IPR = 2)
Time after treatment	1 h	24 h	48 h	72 h	1 h	24 h	48 h	72 h	1 h	24 h	48 h	72 h
CORNEA E= degree of opacity F=area of cornea involved	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0
IRIS D	1	0	0	0	1	0	0	0	1	0	0	0
CONJUNCTIVAE A=Redness B=Chemosis C=Discharge	1 1 1	1 0 1	1 0 0	0 0 0	1 1 1	1 0 1	1 0 0	0 0 0	1 1 1	1 0 1	1 0 0	0 0 0

IPR = Initial Pain Reaction

Table 2: Mean Scores for Ocular Irritation

Skin Reaction	Mean scores for 24, 48 and 72 hours
-	83 Male	26 Male	27 Male
Cornea	0	0	0
Iris	0	0	0
Conjunctivae - redness	2/3 = 0.67	2/3 = 0.67	2/3 = 0.67
Conjunctivae – chemosis	0	0	0

No corneal effects were noted during the study.

Iridial inflammation was noted in all treated eyes on hour after treatment.

Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48 -hour observations.

All treated eyes appeared normal at the 72 hour observation.

Interpretation of results:

GHS criteria not met

Conclusions:

There were no corneal or iridial effects or chemosis noted during the study after 24 hours of exposure; hence, the mean scores for 24, 48 and 72 hours for each animal were 0. The mean scores for 24, 48 and 72 hours for each animal for conjunctivae redness, although above 0, were below the limits for classification as irritating to eyes (Category 2) and the effects were fully reversible within an observation period of 21 days. PCC is therefore non-irritating to eyes and does not require classification according to the criteria described in Regulation (EC) No 1272/2008.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Common functional groups/mechanism of action.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target: Lime (chemical) hydraulic [CAS 85117-09-5; See section 1.2 for information on purity.
Source: calcium dihydroxide [CAS 1305-62-0; EC 215-137-3] purity not stated, but lab grade.

3. ANALOGUE APPROACH JUSTIFICATION
When administered to the eyes for testing irritating properties (moistened with water, according to the test guideline EC B.4), the main constituent of lime (chemical) hydraulic, calcium hydroxide 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 lime (chemical) hydraulic involved in skin irritation. In view of the fact that both calcium hydroxide and lime (chemical) hydraulic 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 lime (chemical) hydraulic has been determined at 12.3 (see section 4.8, O'Connor and Woolley, 2010), whereas Ca(OH)2 creates a pH value of 12.4 (Fox, 2010b). Therefore, local effects due to lime (chemical) hydraulic will be approximately equivalent to those arising from Ca(OH)2.

4. DATA MATRIX
Source: No studies available
Target: Category 1

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hour after administration

Score:

4

Max. score:

4

Reversibility:

not specified

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:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons after the 1 hour observation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour after administration

Score:

3

Max. score:

4

Reversibility:

not specified

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:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons after the 1 hour observation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour after administration

Max. score:

2

Reversibility:

not specified

Remarks on result:

not determinable

Remarks:

iris not visible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons after the 1 hour observation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons after the 1 hour observation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

The results of an available in vivo skin irritation studies (rabbit) indicate that lime (chemical) hydraulic may be irritating to skin (pH effect), by read-across from Ca(OH)2. In vivo data show that calcium carbonate is not a skin irritant. Applying the generic concentration limits specified in table 3.2.3 of the CLP guidance indicates that all grades of lime (chemical) hydraulic, including those containing up to 40% calcium carbonate would be classified as Skin Irritant 2.

In the available eye irritation study (in vivo, rabbit), Ca(OH)2 caused irreversible lesions in the eye. By read across the results are also applicable for hydraulic lime. In vivo data show that calcium carbonate is not an eye irritant. Applying the generic concentration limits specified in table 3.3.3 of the CLP guidance indicates that all grades of lime (chemical) hydraulic, including those containing up to 40% calcium carbonate would be classified as Eye Damage 1.

From human data on calcium oxide and hydroxide it is concluded by read-across (worst case approach) that lime (chemical) hydraulic is irritating to the respiratory tract. No data are available for calcium carbonate, however based on its non-irritancy to skin and eyes, it would not be expected to be a respiratory irritant. Applying the generic concentration limits mentioned in table 3.8.3 of the CLP guidance indicates that all grades of lime (chemical) hydraulic, including those containing up to 40% calcium carbonate would be classified as STOT SE 3.

Justification for classification or non-classification

Based on experimental results on a similar substance utilised by read-across, lime (chemical) hydraulic requires classification as irritating to skin [Skin Irrit 2 (H315 – Causes skin irritation)].

Based on experimental results on a similar substance utilised by read-across, lime (chemical) hydraulic requires classification as severely irritating to the eye [Eye Damage 1 (H318 - Causes serious eye damage)].

Based on human data as summarised and evaluated in the SCOEL recommendation (Anonymous, 2008: Recommendation from the Scientific Committee on Occupational Exposure Limits for Calcium oxide (CaO) and calcium hydroxide (Ca(OH)2), European Commission, DG Employment, Social Affairs and Equal Opportunities, SCOEL/SUM/137 February 2008, see section 7.2.2 of the technical dossier), it is proposed to classify lime (chemical) hydraulic as irritating to the respiratory system [STOT SE 3 (H335 - May cause respiratory irritation)].