Aluminium hydroxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

: No details were provided on the method used to measure the pH. The pH of the tested Al(OH)3/SH-20 Muster was reported as 5.0.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium hydroxide

EC Number:

244-492-7

EC Name:

Aluminium hydroxide

Cas Number:

21645-51-2

Molecular formula:

AlH3O3

IUPAC Name:

aluminum trihydroxide

Constituent 2

Reference substance name:

Aluminium hydroxide / SH-20 Muster

IUPAC Name:

Aluminium hydroxide / SH-20 Muster

Details on test material:

Name: Aluminium hydroxide/SH-20 MusterBatch No.: 40/2009CAS No.: 21645-51-2Appearance: Powder/white or light greyPurity: “suitable chemical purity”(p.9)Storage conditions: Room temperature (15-25°C)Manufacture date: 19 March 2009-11-04 Expiry date: UnlimitedSafety precautions: Routine safety precautions (gloves, goggles, face mask, lab coat) Source: Aluminium Oxid Stade GmbHpH of the test item- 5.0

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test animals:Species and strain: New Zeland White rabbitsSex: male Source: S&K-LAP Kft., 2173 Kartal, Császár út 135, HUNGARYAge at study initiation: 10 weeks old Body weight range at the beginning of the study: 2681-2838 g.Body weight range at the end of study: 2782-2969 g.Data of receipt: 26 August 2009Acclimation: 5 days Identification: Individual identification by engraved ear tags. The cages were marked with individual identity cards with information about study code, sex, cage number, dose group and individual animal number.Environmental/housing and feeding conditions:Lighting period: 12/12 cycleTemperature:18.2± 22.0 oCRelative humidity: 40-68%Housing/Enrichment: Rabbits were individually housed in AAALC approved metal wire rabbit cages (65x65 cm with height of 45 cm, on 2 levels with a shelf to allow rabbits to climb up to stretch out). Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.Ventilation: 15-20 air exchange/hourThe environmental parameters were recorded twice daily during the acclimatisation and experimental phases.Feeding conditionsDiet: The diet PURINA Base _ Lap gr . diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum. Contents of PURINA Base – Lap gr. diet for rabbits provided.Water: The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.The drinking water was routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. The quality control analysis was performed once every three months and microbiological assessment is performed monthly by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary).

Test system

Vehicle:

other: The test item was used as a powder.

Controls:

other: The contralateral eye served as the control.

Amount / concentration applied:

0.1g of Aluminium Hydroxide was instilled into the conjunctival sac of the left eye to each animal(no vehicle) . The eyelids were held closed for several seconds to prevent the loss of the test item.

Duration of treatment / exposure:

The eyes were washed out with 0.9% saline at 1 hour after application of test substance.

Observation period (in vivo):

Animals examined at 1, 24, 48 and 72 hours after treatment. Immediately after administration, the initial pain reaction was assessed according to the 6 point scale (see below).Any clinical signs of toxicity or signs of ill- health during the study were recorded.Individual reactions of the animal were recorded at each observation time. The nature, severity and duration of all lesions observed were described.

Number of animals or in vitro replicates:

3 males per group

Details on study design:

REMOVAL OF TEST SUBSTANCE- Washing (if done): : the test item was removed by washing 1 hour after exposure.- Time after start of exposure:SCORING SYSTEM: Draize scoring systemAdditional information:Care was taken to select only those animals that had a normal eye condition and any with ocular lesions were rejected.An initial test was performed using one animal. The test item was instilled into the conjunctival sac of the left eye. The eyelids were held closed for several seconds to prevent the loss of the test item. The contralateral eye served as the control. Immediately after the administration of the test item, an assessment of the initial pain reaction was made according to the six point scale.After consideration of the ocular responses produced in the first animal, two additional animals were treated.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

3

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

3

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

3

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

2

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

2

Results 9

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

3

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

Initial pain reaction (IPR) (score I) was observed in two animals, IPR (score 2) – in one animal. At observation one hour after the application, conjunctival redness (score 2) was observed in all animals, conjunctival discharge (score 2) in one and conjunctival discharge (score 1) was found in two animals.At 24 after the treatment, two animals showed slight redness (score 1).At 48 hours after treatment full recovery was observed.At 72 hours after treatment, there were no clinical signs observed. As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hour observation.During the study, the control eye of animals was symptom-free.

Other effects:

MortalityThere was no mortality observed during the study.Body weightThere was no effect of treatment on body weight.Clinical observation/General Daily ExaminationThere were no treatment-related clinical signs noted.

Any other information on results incl. tables

MEAN VALUES OF EYE IRRITATION

(24, 48, 72 hour reading)

 

Study Code:    09/164-005N                       Species:    NZW Rabbit

Dose:                                               Sex:          Male

Start of Exposure:                                     31 August 2009 – Day 0                    Aluminium Hydroxide

 

Animal Number	Sex	Cornea Opacity	Iris	Conjunctivae
				Redness	Chemosis	Discharge
00911	male	0.00	0.00	0.33	0.00	0.00
00974	male	0.00	0.00	0.33	0.00	0.00
00908	male	0.00	0.00	0.00	0.00	0.00

 

 

INDIVIDUAL SCORES FOR OCULAR IRRITATION

 

 

Abbreviations:              R     =   Redness            OD   =     Opacity degree of density

                                      CH   =   Chemosis               OE   =     Extension of opaque area

D     =     Discharge           IPR   =     Initial pain reaction

NT    =     Can not be scored    -     =     No data

 

Time of Observation: 1, 24, 48 and 72 hour reading

 

Time	Animal No.	Score of irritation								IPR
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
1 hour	00911	2	0	1	0	0	0	0	-	2
	00974	2	0	1	0	0	0	0	-	1
	00908	2	0	2	0	0	0	0	-	1

Time of Observation: Day 0

Time	Animal No.	Score of irritation								IPR
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
1 hour	00911	2	0	1	0	0	0	0	-	2
	00974	2	0	1	0	0	0	0	-	1
	00908	2	0	2	0	0	0	0	-	1

 

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
24 hours	00911	1	0	0	0	0	0	0	-
	00974	1	0	0	0	0	0	0	-
	00908	0	0	0	0	0	0	0	-

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
48 hours	00911	0	0	0	0	0	0	0	-
	00974	0	0	0	0	0	0	0	-
	00908	0	0	0	0	0	0	0	-

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
72 hours	00911	0	0	0	0	0	0	0	-
	00974	0	0	0	0	0	0	0	-
	00908	0	0	0	0	0	0	0	-

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

An acute eye irritation study of the test item Aluminium Hydroxide was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

Executive summary:

An acute eye irritation study of the test item Aluminium Hydroxide was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. An amount of the test item was administered as a single dose. The eyes of the test animals were washed out at one hour after the application of the test item.

 

The eyes were examined at 1, 24, 48, 72 hours after the application.

 

Initial Pain Reaction (IPR) (score 1) was observed in two animals, IPR (score 2) in one animal.

 

One hour after the application, conjunctival redness (score 2) was observed in all animals, conjunctival discharge (score 2) in one and conjunctival discharge (score 1) was found in two animals.

 

At 24 hours after treatment: two animals showed slight redness (score 1).

 

At 48 hours after treatment: full recovery was observed.

 

At 72 hours after treatment: there were no clinical signs observed.