Calcium carbonate

Endpoint summary

Description of key information

Bulk calcium carbonate is not considered to be irritating to the skin or eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key 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)

Specific details on test material used for the study:

Bulk calcium carbonate

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:

other: 24, 48 and 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:

edema score

Basis:

other: Mean scores for all animals

Time point:

other: 24, 48 and 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 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:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key 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:

other: 24, 48 and 72 hours

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:

other: 24, 48 and 72 hours

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:

other: 24, 48 and 72 hours

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:

other: 24, 48 and 72 hours

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:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In a reliable GLP OECD guideline 404 in vivo skin irritation study (Sanders, 2004), 0.5 g bulk calcium carbonate was applied to the shaved skin of 3 New Zealand White rabbits under a semiocclusive patch for 4 hours. Animals were observed after removal of the patch at 1, 24, 48 and 72 h. The average of the erythema and edema assessments for the 3 animals after 72 h was 0.0. Therefore, calcium carbonate was found to be non-irritating to the skin in rabbits.

Eye irritation:

In a reliable GLP OECD guideline 405 in vivo eye irritation study (Sanders, 2004), ~100 mg bulk calcium carbonate was instilled into the eyes of 3 New Zealand White rabbits. Ocular observations were made at 1, 24, 48 and 72 h after instillation.

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.

From the results of this study, bulk calcium carbonate does not need to be classified as irritating to the eyes.

Justification for classification or non-classification

In the in vivo skin and eye irritation studies bulk calcium carbonate was non-irritant and therefore requires no classification under CLP.