Dialuminum tetramagnesium carbonate dodecahydroxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed similar to OECD 404 guideline but without GLP. Limited information on test material and environmental conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

The primary skin-stimulation effect of DHT-4A in rabbits was investigated according to Draize's rating scale.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium magnesium carbonate hydroxide

EC Number:

943-434-4

Cas Number:

11097-59-9

Molecular formula:

[Al2Mg4(OH)12] CO3

IUPAC Name:

Aluminium magnesium carbonate hydroxide

Details on test material:

Chemical Formula: Mg4.5AL2(OH)13CO3 3.5H2O
Chemical nomenclature: Hydrotalcite DHT-4A

Test animals

Species:

rabbit

Strain:

other: white male Japanese rabbits (Yugengaisha Ichikaway)

Details on test animals or test system and environmental conditions:

Six healthy white male Japanese rabbits, weighing approximately 3 Kg (2.55-3.12kg), were used in this study. Solid food manufactured by Clea Japan Inc. (CR-1) and normal drinking water in a bottle were taken ad libitum.

Test system

Type of coverage:

occlusive

Preparation of test site:

other: shaved excoriated and unexcoriated sites

Vehicle:

not specified

Controls:

no

Amount / concentration applied:

The test drug, 500 mg, undiluted or its 10% solution, 0.5 mL, on a 4x4 cm lint patch was fixed tightly to the skin at 4 sites of each rabbit.

Duration of treatment / exposure:

24 hours

Observation period:

Further observations and evaluation were made at the 48th and 72nd hours, as well as on the 5th and 7th day.

Number of animals:

6

Details on study design:

The experiment was carried out as follows:
(a) Six rabbits were seared on the back , where 4 sites, larger than 5 x Scm each, were tested .
(b) Two diagonal sites of the four were scored in across -hatched pattern with a sterilized wire brush for destruct ion of the corneum. The injury was slight lest the corium should be impaired or bleeding should occur.
(c) The skin of two other sites was not excoriated.
(d) The test drug , 500mg , undiluted or i ts 10% solution, 0.5 ml , on a 4 x 4cm lint patch, wa s fixed tightly to the skin at the 4 sites of each rabbit .
(e) After a 24 -hours, the patches were removed and evaluation was made; thereafter, the sites were cleansed with water.
(f) Further observation and evaluation were made at the 48th and 72nd hours, as well as on the 5th and 7th days.
(g) The primary stimulating rate was calculated as a mean o f erythema and edema scores at 12 sites - 6 excoriated and 7 intact - at the 24th and
72th hours.
(h) After prognostic observation was made up to the 7th day, all animals were killed and the subcutaneous tissue under the testsites examined ;
the skin was then removed and fixed in a formalin solution for preservation .

Judgement of Results:
The results were graded according to Draize's rating scale.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1, #2, #3, #4, #5 and #6

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: Undiluted on excoriated site

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1, #2, #3, #4, #5 and #6

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: Undiluted on excoriated site

Results 3

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1, #2, #3, #4, #5 and #6

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: Undiluted on unexcoriated site

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1, #2, #3, #4, #5 and #6

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Undiluted on unexcoriated site

Results 5

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1, #2, #3, #4, #5 and #6

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: 10% dilution on excoriated site

Results 6

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1, #2, #3, #4 and #6

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: 10% dilution on excoriated site

Results 7

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: 10% dilution on excoriated site

Results 8

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1, #2, #3, #4, #5 and #6

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: 10% dilution on unexcoriated site

Results 9

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: 10% dilution on unexcoriated site

Results 10

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2, #3, #4, #5 and #6

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: 10% dilution on unexcoriated site

Irritant / corrosive response data:

Experimental Results

The skin findings attributable to DHT-4A undiluted or to its 10% solution , chiefly involved edema.
1. A 10% DHT-4A Solution
1) Unexcoriated sites
No significant change was observed, except very slight edema in one of the six cases at the 24th hour of treatment.
The edema disappeared 48 hours after the solution was applied.
2) Excoriated sites
Except for very slight edema in 5 of the six cases at the 24th hour o f treatment, no particular change was noted .
The edema cleared up 48 hours a fter the solution was applied.

2. DHT- 4A Undiluted
1) Unexcoriated sites
After the 24th and 48th hours of application , neither erythema nor edema was seen , and no abnormal findings were noted .
2 ) Excoriated sites
There were no particular changes other than very slight edema observed in any cases 24 hours a fter application .
The edema cleared up 48 hours after application.

Other effects:

In the animals killed at the end of the trial period, no abnormal findings were noted on the subcutaneous tissue under the test sites, or in any organ.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

This study of the primary skin-stimulating effects of DHT- 4A undiluted and 10% DHT-4A performed similar to OECD 404 guideline, indicated that DHT-4A (undiluted and 10% dilution) showed only very slight edema 24 hours after application, even at excoriated sites. The edema effects were fully reversible 48 hours after application.

Executive summary:

This study of the primary skin-stimulating effects of DHT- 4A undiluted and 10% DHT-4A using 6 male rabbits was performed similar to OECD 404 guideline.

DHT-4A (undiluted and 10% dilution) showed only very slight edema 24 hours after application. The edema effects were fully reversible 48 hours after application, even at excoriated sites.

In the animals killed at the end of the study, no abnormal findings were noted on the subcutaneous tissue under the test sites, or in any organ. Based on the results, DHT-4A does not have to be classified for skin irritation according to Regulation (EC) No 1272/2008.