Calcium carbonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 January 2010 - 20 January 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Calcium carbonate

EC Number:

207-439-9

EC Name:

Calcium carbonate

Cas Number:

471-34-1

Molecular formula:

CH2O3.Ca

IUPAC Name:

calcium carbonate

Test material form:

solid: nanoform, no surface treatment

Details on test material:

- Name of test material (as cited in study report): Calcium carbonate (nano)
- Description: White powder
- Batch No.: GICM014427
- Storage condition of test material: Room temperature in the dark

The nano form of calcium carbonate was tested because this form was anticipated to represent the worst case as the smaller size particles are more likely to be transported through the skin.

Specific details on test material used for the study:

Uncoated nano calcium carbonate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: at least 200 g
- Fasting period before study: No data
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Food (2014 Teklad Global Rodent diet) was available ad libitum.
- Water (e.g. ad libitum): Mains drinking water was available ad libitum.
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks of each animal
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material.
- Time after start of exposure: 24 h


TEST MATERIAL
The appropriate amount of test material, moistened with arachis oil BP, was applied as evenly as possible to an area of shorn skin using a graduated syringe.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals/ sex/ dose

Control animals:

not specified

Details on study design:

The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the scale from Draize (1977).

Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.

At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity or dermal irritation.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual clinical observations and mortality data

Dose level (mg/kg)	Animal no. & sex	Effects noted after initiation of exposure (hours)				Effects noted after initiation of exposure (days)
		0.5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	Males (1-1, 1-2, 1-3 & 1-4)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Females (2-1, 2-2, 2-3 & 2-4)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = no signs of systemic toxicity

 

 

Table 2: Individual dermal reactions – Males

Dose level (mg/kg)	Animal no. & sex	Observation	Effects noted after initiation of exposure (days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	Males (1-1, 1-2, 1-3 & 1-4)	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = No reactions

 

 

Table 3: Individual dermal reactions – Females

Dose level (mg/kg)	Animal no. & sex	Observation	Effects noted after initiation of exposure (days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	Females (2-1, 2-2, 2-3 & 2-4)	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = No reactions

 

 

Table 4: Individual bodyweights and weekly bodyweight changes

Dose level (mg/kg)	Animal no. & sex	Bodyweight (g) at Day			Bodyweight change (g) during week
		0	7	14	1	2
2000	1-0 Male	232	256	278	24	22
	1-1 Male	235	255	270	20	15
	1-2 Male	242	268	288	26	20
	1-3 Male	224	246	270	22	24
	1-4 Male	234	261	279	27	18
	2-0 Female	220	228	239	8	11
	2-1 Female	203	204	216	1	12
	2-2 Female	211	216	218	5	2
	2-3 Female	217	220	230	3	10
	2-4 Female	212	213	220	1	7

 

 

Table 5: Individual necropsy findings

Dose level (mg/kg)	Animal no. & sex	Macroscopic observations
2000	Males (1-1, 1-2, 1-3 & 1-4)	No abnormalities detected
	Females (2-1, 2-2, 2-3 & 2-4)	No abnormalities detected

 

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.