Dialuminum tetramagnesium carbonate dodecahydroxide

Endpoint summary

Description of key information

The registered substance (DHT-4A):
Skin irritation:
Study performed similar to OECD 404. It was concluded that the substance is not irritating to skin.
Eye irritation
Eye stimulating effects were very slight, as all symptoms were eliminated  within 48 hours. 
Read-across:
Alcamizer 5 (EC 422-150-1) and Aluminium-magnesium-zinc-carbonate-hydroxide (EC 423-570-6):
Skin irritation: Not irritating.
Eye irritation: Mildly irritating

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:

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.

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

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.

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.

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

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

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

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

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

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

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

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

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

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.

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.

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:

March 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed similar to OECD 405 guideline but without GLP. Limited information on test material and environmental conditions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

The extent of DHT-4A ocular mucous membrane-stimulating effects were investigated in rabbits using the Draize's rating scale.

GLP compliance:

no

Species:

rabbit

Strain:

other: male Japanese rabbits (Yugengaisha Ichikaway)

Details on test animals or tissues and environmental conditions:

Healthy white Japanese rabbits weighing approximately 3kg (Yugengaisha I chikawaya ) were used for this study .
All were male, totaling 9. Solid food manufactured by Clea Japan Inc. (CR-l) and normal drinking water in a bottle were taken ad libitum.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg of undiluted test drug was dropped into the everted lower lid;
upper and lower lids were separated after light contact.

Duration of treatment / exposure:

The rabbits were divided into the 3 whose eyes were not washed after treatment, the 3 those whose eyes were washed with 20ml of mild warm water 2 seconds after treatment, and the 3 those whose eyes were washed with 20 ml of tepid water 4 seconds after treatment.

Observation period (in vivo):

All rabbits were observed 1, 2, 3, 4 and 7 days later and evaluated according to rating criteria.

Number of animals or in vitro replicates:

9

Details on study design:

The experiment was carried out according to the following procedure .
(a ) Nine white male Japanese rabbits (weighing approximately 3kg ) , adjudged normal following a cornea test with fluorescein paper (Haag-streit ag
liebefed-dern Switzerland) were used .
(b) The test drug was dropped into the right eye, the left eye being left untreated for comparison. 100 mg of undiluted test drug was dropped into the everted lower lid; upper and lower lids were separated after light contact.
(c) The rabbits were divided into the 3 whose eyes were not washed after treatment, the 3 those whose eyes were washed with 20ml of mild warm
water 2 seconds after treatment,and the 3 those whose eyes were washed with 20 mL of tepid water 4 seconds after treatment.
(d) all the rabbits were observed 1,2,,3,4, and 7 days later and evaluated according to rating criteria.
(e) after 7- days of observation the animals were killed for autopsy; the upper and lower eyelids, nicititating membranes eyeballs and optic nerves were removed and preserved in formalin fixative.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: overall 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: eyes not washed

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: overall 24, 48 and 72 h

Score:

0

Max. score:

2

Remarks on result:

other: eyes not washed

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

animal #1 and #3

Time point:

other: overall 24, 48 and 72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: eyes not washed

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: overall 24, 48 and 72 h

Score:

0

Max. score:

3

Remarks on result:

other: eyes not washed

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1 and #2

Time point:

other: overall 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: eyes not washed

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: overall 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: eyes not washed

Irritant / corrosive response data:

In ocular response to DHT-4A undiluted, chief symptoms were conjunctival changes , whereas there were no changes in the cornea or iris.

1. Rabbits whose eyes were not washed
On the first day of eye - dropping, accelerated congestion of the conjunctiva was noted in two of the three rabbits,
while exaggerated conjunctival edema and excess discharge were observed in the other .
However, on the second day of eye-dropping , conjunctival congestion , edema and discharge began to disappear .

2. Rabbits whose eyes were washed 2 seconds after treatment.
On the first day of eye-dropping, excessive discharge was observed in two out of the three.
On the second day of eye-dropping , such disc harge began to cease.

3 . Rabbits whose eyes were washed 4 seconds after treatment .
On the first day of eye-dropping, accelerated conjunctival congestion was noticed in two of the three rabbits, but it disappeared on the second day.

Other effects:

In all the animals killed at the end of the test period , there were no significant changes in the upper or lower lids ,
nictitating membranes, eye balls , optic nerves or other organs.

In ocular response to DHT-4A undiluted, chief symptoms were conjunctival changes , whereas there were no changes in the cornea or iris.

1. Rabbits whose e yes were not washed

On the first day of eye - dropping, accelerated congestion of the conjunctiva was noted in two of the three rabbits,

while exaggerated conjunctival edema and excess discharge were observed in the other .

However, on the second day of eye-dropping , conjunctival congestion , edema and discharge began to disappear .

2. Rabbits whose eyes were washed 2 seconds after treatment.

On the first day of eye-dropping, excessive discharge was observed in two out of the three.

On the second day of eye-dropping , such disc harge began to cease.

3 . Rabbits whose eyes were washed 4 seconds after treatment .

On the first day of eye-dropping, accelerated conjunctival congestion was noticed in two of the three rabbits, but it disappeared on the second day.

Interpretation of results:

slightly irritating

Remarks:

Migrated information The very slight effects were fully reversible 48 hours after application. Criteria used for interpretation of results: EU

Conclusions:

This study of the primary stimulating effect of DHT- 4A on the ocular mucous membrane of the rabbit performed similar to OECD 405 guideline, indicated that DHT-4A showed very slight conjunctivae in 2 animals and very slight chemosis in one animal. The effects were fully reversible 48 hours after application.

Executive summary:

This study of the primary stimulating effect of DHT- 4A on the ocular mucous membrane of the rabbit performed similar to OECD 405 guideline.

DHT-4A showed very slight conjunctivae in 2 animals and very slight chemosis in one animal. The effects were fully reversible 48 hours after application. Based on the results, DHT-4A does not have to be classified for eye irritation according to 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

For details see specific end point study record. All information indicated that hydrotalcite-like compounds are not irritating to skin and slightly irritating to the eye. The substance Aluminium magnesium carbonate hydroxide does not cause eye irritation leading to classification of the substance.  

EC #	423-570-6	422-150-1	Not yet assigned
Name	P93	Alcamizer 5	DHT-4A (Aluminium magnesium carbonate hydroxide)
Skin irritation	not irritating	not irritating	not irritating
Eye irritation	mildly irritating	mildly irritating	very slightly irritating

 

Justification for selection of skin irritation / corrosion endpoint:
The substance showed no irritation.

Justification for selection of eye irritation endpoint:
The substance showed very slight irritation but not sufficient for classification.

Justification for classification or non-classification

Based on the results of the studies performed with the substance and substance analogues, the substance Aluminium magnesium carbonate hydroxide

does not have to be classified for skin irritation or eye irritation according to Regulation (EC) No 1272/2008.