Indium trihydroxide

Endpoint summary

Description of key information

key studies demonstrate a lack of irritation/corrosion potential

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)

Version / remarks:

version 13 April 2004

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

skin obtained from plastic surgery from multiple donors

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN-SM (Manufacturer: SkinEthic, France, Catalogue Number: EPISKIN/S/13
- Tissue batch number(s): 11-EKIN-042
- Expiry date: 21 November 2011
- Date of initiation of testing: 17 November 2011

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 18-28°C
- Temperature of post-treatment incubation (if applicable): not applicable

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 1wahsing step: rinsing thoroughly with PBS 1x solution (0.9%)

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 2.2 mL of 0.3 mg/mL MTT
- Incubation time: 3h
- Spectrophotometer: 96-well plate spectrophotometer
- Wavelength: 540nm

NUMBER OF REPLICATE TISSUES:3

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE (see any other info on mat and meth)


PREDICTION MODEL / DECISION CRITERIA (choose relevant statement):

- The test substance is considered to be corrosive to skin, if the mean relative viability after 4 hours of exposure is below 35% of the negative control.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

yes, concurrent MTT non-specific colour control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20 mg

VEHICLE
- Amount(s) applied (volume or weight with unit): na; no formulation was required

NEGATIVE CONTROL: NaCI (9 g/l saline)
- Concentration (if solution): 50µl

POSITIVE CONTROL: glacial acetic acid
- Concentration (if solution): 50µl

Duration of treatment / exposure:

4h

Number of replicates:

3

Irritation / corrosion parameter:

other: other: % viability

Run / experiment:

1

Value:

96

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

The results of the optical density (OD) measured at 540 nm of each extract and the calculated % viability of the cells is presented below:

 

Substance	Optical Density (OD)		Viability (%)
Negative Control: NaCl (9g/L saline)	1	0.208	100
	2	0.188
	3	0.192
	mean	0.196
Positive Control: Glacial acetic acid	1	0.011	6
	2	0.008	4
	3	0.025	13
	mean	0.015	8
Test Item: Indium trihydroxide	1	0.195	99
	2	0.191	98
	3	0.181	92
	mean	0.189	96

 

Interpretation of results:

GHS criteria not met

Conclusions:

In this in vitro EPISKIN model test with Indium trihydroxide, the results indicate that the test item is not a skin corrosive.

Executive summary:

Disks of EPISKIN (three units / chemical) were treated with test item Indium trihydroxide and incubated for 4 hours at room temperature. Exposure of test material was terminated by rinsing with PBS 1x solution (0.9 %). The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution. The formazan precipitated was then extracted using acidified isopropanol and quantified spectrophotometrically. NaCI (9 g/l saline) and glacial acetic acid treated epidermis were used as negative and positive controls respectively. For each treated tissue viability was expressed as a % relative to negative control.

The test substance is considered to be corrosive to skin, if the mean relative viability after 4 hours of exposure is below 35% of the negative control.

The test item did not show significantly reduced cell viability in comparison to the negative control. All test item results were far above 35% of the mean negative control value.

In this in vitro EPISKIN model test with Indium trihydroxide, the results indicate that the test item is not a skin corrosive.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

version 24 April 2002

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: ~12 weeks old
- Weight at study initiation: 3033-3071 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages (65x65 cm with height of 45 cm). Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet: Animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum
- Water: municipal tap water, as for human consumption, ad libitum, from an automatic system.
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.1-20.7 °C
- Humidity (%): 24-60%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5g

Duration of treatment / exposure:

4 hours

Observation period:

72h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 6 cm² area of intact skin

REMOVAL OF TEST SUBSTANCE
- Washing: the remaining test item was removed with water at body temperature
- Time after start of exposure: After 4 hours

SCORING SYSTEM:

The dermal irritation scores were evaluated according to the scoring system by Draize (1959)

SCORING SYSTEM OF ERYTHEMA AND OEDEMA FORMATION

Erythema and eschar formation

No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

Maximum possible erythema score: 4

Oedema formation

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of it will be well defined
by definite raising) 2
Moderate oedema (raised appr. 1 mm) 3
Severe oedema (raised more than 1 mm and extending
beyond area of exp.) 4

Maximum possible oedema score: 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals #1, #2, #3

Time point:

other: 1h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals #1, #2, #3

Time point:

24 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals #1, #2, #3

Time point:

48 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals #1, #2, #3

Time point:

72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals #1, #2, #3

Time point:

other: 1h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals #1, #2, #3

Time point:

24 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals #1, #2, #3

Time point:

48 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals #1, #2, #3

Time point:

72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Other effects:

MORTALITY : no mortality observed during the study.
BODY WEIGHTS: no effect of treatment on body weight.
CLINICAL OBSERVATION

General Daily Examination: no treatment-related clinical signs noted.

Examination of Skin-Irritancy:

At observation one, 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals.

As no clinical signs were observed the study was terminated after the 72 hours observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively.

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

SCORING OF ERYTHEMA FORMATION

 

 

TABLE 1

 

Animal No./ Sex	Body weight (g)		1 h	24 h	48 h	72 h
	at the beginning of the study	at the end of the study
00117/ M	3071	3130	0	0	0	0
00146/M	3067	3112	0	0	0	0
00147/M	3033	3091	0	0	0	0
TOTAL	-	-	0	0	0	0
MEAN	-	-	0	0	0	0

 

 

 

 

SCORING OF OEDEMA FORMATION

 

 

TABLE 2

 

Animal No./ Sex	Body weight (g)		1 h	24 h	48 h	72 h
	at the beginning of the study	at the end of the study
00117/ M	3071	3130	0	0	0	0
00146/M	3067	3112	0	0	0	0
00147/M	3033	3091	0	0	0	0
TOTAL	-	-	0	0	0	0
MEAN	-	-	0	0	0	0

 

 

M   = male

d     = day

h     = hour

 

 

MEAN VALUES OF SKIN IRRITATION SCORES

(24, 48, 72 hours reading)

 

TABLE 3

 

 

Animal Number	Sex	Erythema	Oedema
00117	male	0.00	0.00
00146	male	0.00	0.00
00147	male	0.00	0.00

 

 

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, indium trihydroxide does not require classification as a skin irritant.

 

Executive summary:

An acute skin irritation study was performed with Indium trihydroxide in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the Draize method (OECD No.: 404, 2002)

A weight of 0.5g granules test item was applied to the skin of the experimental animals as ground to a powder. The test item was applied as a single dose. Sufficient water to damp the material was used to ensure good contact with the skin and an adhesive clear plastic patch was applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.

After 4 hours, the remaining test item was removed with water at body temperature.

To assess skin irritation, animals were examined at 1, 24, 48 and 72 hours after the patch removal. Additional general examinations were performed daily.

 

There was no mortality or systemic clinical changes related to Indium trihydroxide administration.

 

There was no effect of treatment on body weight.

 

At observation one, 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals.

 

As no clinical signs were observed the study was terminated after the 72 hours observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively.

 

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

 

According to Directive 2001/59/EC,Indium trihydroxide does not require classification as a skin irritant.

 

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals,Indium trihydroxide does not require classification as a skin irritant.

 

According to the classification system based on the scheme devised by Draize (1959),Indium trihydroxide is a "non irritant".

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants)

Version / remarks:

version 7th September 2009

GLP compliance:

yes (incl. QA statement)

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 30mg

Duration of treatment / exposure:

10 seconds

Duration of post- treatment incubation (in vitro):

up to 240 minutes (at 30, 75, 120, 180 and 240 min) after post-treatment rinse for the cornea thickness and cornea opacity
Fluorescein retention was measured at base line (t=0) and at 30 minutes after rinse.

Number of animals or in vitro replicates:

3 test item treated eyes, 3 positive control treated eyes and 1 negative control eye

Details on study design:

SELECTION AND PREPARATION OF ISOLATED EYES
Eyes selection:
After removing the head from the plastic box, it was put on soft paper. The eyelids were carefully cut away with scissors, avoiding damaging the cornea. One small drop of fluorescein solution 2 (v/v) % was applied onto the cornea surface for a few seconds and subsequently rinsed off with 20 ml isotonic saline. Then the fluorescein-treated cornea was examined with hand-held slit lamp or slit lamp microscope, with the eye in the head, to ensure that the cornea was not damaged. If the cornea was in good condition, the eyeball was carefully removed from the orbit.
Preparation of eyes:
The eye ball was carefully removed from the orbit by holding the nictitating membrane with a surgical forceps, while cutting the eye muscles with bent scissors. Care was taken to remove the eyeball from the orbit without cutting off the optical nerve too short. The procedure avoided pressure on the eye while removing the eyeball from the orbit, in order to prevent distortion of the cornea and subsequent corneal opacity. Once removed from the orbit, the eye was placed onto damp paper and the nictitating membrane was cut away with other connective tissue. The prepared eyes were kept on the wet papers in a closed box so that the appropriate humidity was maintained.

EQUILIBRATION AND BASELINE RECORDINGS
At the end of the acclimatization period (45-60min), a zero reference measurement was recorded for cornea thickness and opacity to serve as a base line (t=0) for each individual eye. The cornea thickness of the eyes should not increase by more than 5-7 % between the -45 and the zero time. Slight changes in thickness (-1% to 1%) were observed in the eyes, this is considered normal when maintaining enucleated eyes. Following the equilibration period, the fluorescein retention was measured. Base line values were required to evaluate any potential test item related effect after treatment. All eyes were considered to be suitable for the assay.

NUMBER OF REPLICATES
3 test item treated eyes, 3 positive control treated eyes and 1 negative control eye

NEGATIVE CONTROL USED
treated with 30µL isotonic saline

SOLVENT CONTROL USED (if applicable): not applicable

POSITIVE CONTROL USED
treated with 30 mg imidazole

APPLICATION DOSE AND EXPOSURE TIME
test substance treated chicken eye: treated with 30 mg during 10 seconds

OBSERVATION PERIOD
30, 75, 120, 180 and 240 min after post-treatment. The cornea thickness and cornea opacity were measured at all time points.
Fluorescein retention was measured on two occasions, at base line (t=0) and 30 minutes after the post-treatment rinse.

REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: cornea surface was rinsed thoroughly with 20ml isotonic saline

METHODS FOR MEASURED ENDPOINTS:

- Corneal opacity: examined with slit lamp microscope
- Damage to epithelium based on fluorescein retention: examined with hand-held slit lamp or slit lamp microscope
- Swelling: examined with slit lamp microscope


SCORING SYSTEM: see below other info on mat and meth
- Mean corneal swelling (%)
- Mean maximum opacity score
- Mean fluorescein retention score at 30 minutes post-treatment
- Histopathology

DECISION CRITERIA: as indicated in the TG

Irritation parameter:

percent corneal swelling

Run / experiment:

up to 75min

Value:

1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Irritation parameter:

percent corneal swelling

Run / experiment:

up to 240min

Value:

3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Value:

0

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Irritation parameter:

fluorescein retention score

Value:

0

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

The mean values of the treated eyes for maximum corneal thickness change, corneal opacity and fluorescein retention are given below. The conclusion on eye irritancy was based on the OECD guideline quantitative assessments.

Test Item: Indium trihydroxide

Observation	Value	ICE Class*
Mean maximum corneal swelling at up to 75 min	1 %	I
Mean maximum corneal swelling at up to 240 min	3 %	I
Mean maximum corneal opacity	0.00	I
Mean fluorescein retention	0.00	I
Other Observations	The Test item was stuck on the cornea surface after the post-treatment rinse. The cornea surface was not cleared 240 min after the post-treatment rinse
Overall ICE Class*	3xI

In this in vitro eye irritation in the isolated chicken eyes test with Indium trihydroxide, the results suggest that the test item was not irritating.No conclusion of in vivo significance can be made from the adherence of the test item to the cornea, since in vivo eye lids will probably clear the surface, but abrasion may occur. An in vivo study is required for classification.

Positive Control: Imidazole

Observation	Value	ICE Class*
Mean maximum corneal swelling at up to 75 min	4 %	I
Mean maximum corneal swelling at up to 240 min	5 %	I
Mean maximum corneal opacity	4.00	IV
Mean fluorescein retention	2.83	IV
Other Observations	The Imidazole was stuck on the cornea surface after the post-treatment rinse. The cornea surface was not cleared 240 minutes after the post-treatment rinse.
Overall ICE Class*	1xI 2xIV

The positive control Imidazole was classed as severely irritating,GHS Classification: Category 1.

Negative Control: Sodium chloride

Observation	Value	ICE Class*
Mean maximum corneal swelling at up to 75 min	0 %	I
Mean maximum corneal swelling at up to 240 min	0 %	I
Mean maximum corneal opacity	0.00	I
Mean fluorescein retention	0.00	I
Other Observations	None
Overall ICE Class*	3xI

The negative control Sodium chloride 0.9% had no significant effects on the chicken eye in this study.

Table:Assessment of the general IN VITRO eye irritancy and regulatory GHS classification.

 

The following table is used to identify the probably eye irritancy potential of test items. In the case where the result indicates Corrosive/Severely Irritating, then the test item can be classified as Severe. In all other cases the probable level of irritancy can be reported, but a regulatory in vivo rabbit eye irritation test is required for regulatory classification and labelling purposes.

EC and GHS Classification	Combinations of the three ICE Classes
A=Not irritating	3×I 2×I, 1×II 2xII, 1xI^4
B= Slightly irritating (GHS^3category 2B: Mild irritant / causes eye irritation)	3×II 2×II, 1×III 1×I, 1×II, 1×III^1
C= Moderately irritating (GHS^3category 2A: Irritant / causes eye irritation)	3×III 2×III, 1×II 2xI, 1xIV^1 2×III, 1×IV^2 2×III, 1×I 2×II, 1×IV^1 1×II, 1×III, 1×IV^1
D= Corrosive/severely irritating (GHS^3category 1: Irreversible effects on the eye / serious damage to the eye)	3×IV 2×IV, 1×III 2×IV, 1×II^1 2×IV, 1×I^1 Corneal opacity ≥ 3 at 30 min (in at least 2 eyes) Corneal opacity = 4 at any time point (in at least 2 eyes) Severe loosening of epithelium (in at least 1 eye)

Interpretation of results:

GHS criteria not met

Conclusions:

In this in vitro eye irritation study in the Isolated Chicken Eyes model with Indium trihydroxide, the results suggest that the test item is not irritating. According to the guideline OECD 438, Indium trihydroxide does not require a classification as a severe eye irritant. Indium trihydroxide remained adhered to the cornea surface after the post-treatment rinse.

Executive summary:

An in vitro eye irritation study of the test item Indium trihydroxide was performed in chicken’s eyes. The irritation effects of the test item were evaluated according to the OECD No.: 438 (07^thSeptember 2009).

 

After the zero reference measurements, the eye was held in horizontal position and 30 mg of Indium trihydroxide was applied onto the centre of the cornea such that the entire surface of the cornea was covered. After 10 seconds, the surface was rinsed with saline. The positive control eyes were treated in a similar way with 30 mg Imidazole. The negative control eye was treated with 30 µL of isotonic saline.

In this in vitro eye irritation study in the Isolated Chicken Eyes model with Indium trihydroxide, the results suggest that the test item is not irritating. According to the guideline OECD 438, Indium trihydroxide does not require a classification as a severe eye irritant. Indium trihydroxide remained adhered to the cornea surface after the post-treatment rinse.

 

 

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

version 24 April 2002

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: ~14 weeks old
- Weight at study initiation: 3620-3916 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages
- Diet: Animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum
- Water: municipal tap water, as for human consumption, ad libitum, from an automatic system.
- Acclimation period: 27 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 24-64%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 100mg

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

The eyes were examined at 1, 24, 48, 72 hours and 1 week after treatment. The study was terminated after the 1-week observation.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): eyes of the test animals were washed out
- Time after start of exposure: at 1 hour after application of test item

SCORING SYSTEM:
The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0.67

Reversibility:

fully reversible within: 1 week

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0.67

Reversibility:

fully reversible within: 1 week

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

1.33

Reversibility:

fully reversible within: 1 week

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

animals’ individual mean scores (considering readings at 24, 48 and 72 hours after treatment)

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 1 week

MORTALITY: no mortality observed during the study.

BODY WEIGHTS: the body weight and body weight change were considered to be normal with no indication of treatment related effect.

CLINICAL OBSERVATION:

General daily examination: no clinical signs observed that could be related to treatment.

Examination of eye-irritancy:

Initial Pain Reaction (IPR) (score 1 or 2) was observed in all animals.

One hour after the application, conjunctival redness (score 1 or 2) and discharge (score 3) were seen in all rabbits.

At 24 hours after treatment conjunctival redness (score 1 or 2) was seen in all rabbits.

At 48 hours after treatment, conjunctival redness (score 1) was seen in all rabbits.

At 72 after treatment, conjunctival redness (score 1) was seen in one rabbit.

At one week after treatment, no signs of eye irritation or other clinical signs were observed.

The study was terminated after the 1-week observation.

During the study, the control eye of each animal was symptom-free.

The general state and behaviour of animals were normal throughout the study period. There were no notable body weight changes during the study period.

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

chemosis : 0.00, 0.00, 0.00

discharge : 0.00, 0.00, 0.00

redness : 0.67, 0.67, 1.33

cornea opacity: 0.00, 0.00, 0.00

iris : 0.00, 0.00, 0.00

TABLE 1:Individual Scores for Ocular Irritation

 

Abbreviations:   R    = Redness                                OD =   Opacity degree of density

                               CH = Chemosis                              OE =   Extent of opaque area

D    = Discharge                              IPR=   Initial pain reaction

 

Time	Animal No.	Score of irritation								IPR
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
1 hour	00387	1	0	3	0	0	0	0	-	2
	00380	2	0	3	0	0	0	0	-	1
	00397	2	0	3	0	0	0	0	-	1

Time of Observation: Days 0 and 1

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
24 hours	00387	1	0	0	0	0	0	0	-
	00380	1	0	0	0	0	0	0	-
	00397	2	0	0	0	0	0	0	-

Time of Observation: Days 1 and 2

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
48 hours	00387	1	0	0	0	0	0	0	-
	00380	1	0	0	0	0	0	0	-
	00397	1	0	0	0	0	0	0	-

Time of Observation: Days 2 and 3

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
72 hours	00387	0	0	0	0	0	0	0	-
	00380	0	0	0	0	0	0	0	-
	00397	1	0	0	0	0	0	0	-

Time of Observation: Days 3 and 4

 

 

 

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
1 week	00387	0	0	0	0	0	0	0	-
	00380	0	0	0	0	0	0	0	-
	00397	0	0	0	0	0	0	0	-

Time of Observation: Days 7 and 8

TABLE 2: Mean Values of Eye Irritation (24, 48, 72 hour reading)

 

 

Animal Number	Sex	Cornea Opacity	Iris	Conjunctivae
				Redness	Chemosis	Discharge
00387	male	0.00	0.00	0.67	0.00	0.00
00380	male	0.00	0.00	0.67	0.00	0.00
00397	male	0.00	0.00	1.33	0.00	0.00

TABLE 3:Body Weight Data

 

 

 

Animal Number	Beginning of study (g)	At the end of study (g)	Body weight gain (g)
00387	3620	3702	82
00380	3724	3896	172
00397	3916	4058	142

 

 

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test item Indium trihydroxide (In(OH)3) (Batch No.: OH-1306), applied to rabbits’ eye mucosa, caused significant conjunctival effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 1 week.
According to Regulation (EC) No 1272/2008, Indium trihydroxide (In(OH)3) does not require classification as an eye irritant.

Executive summary:

An acute eye irritation study of the test item Indium trihydroxide (In(OH)3) 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 0.1 g of the test item was administered as a single dose.

 

Individual body weight was recorded at the beginning and end of the study. Morbidity and clinical signs of toxicity were checked daily. The eyes were examined at 1, 24, 48, 72 hours and 1 week after the application.

 

Initial Pain Reaction(IPR) (score 1 or 2) was observed in all animals.

One hour after the application, conjunctival redness (score 1 or 2) and discharge (score 3) were seen in all rabbits.

At 24 hours after treatment conjunctival redness (score 1 or 2) was seen in all rabbits.

At 48 hours after treatment, conjunctival redness (score 1) was seen in all rabbits.

At 72 after treatment,conjunctival redness (score 1) was seen in one rabbit.

At one week after treatment, no signs of eye irritation or other clinical signs were observed.

The study was terminated after the 1-week observation.

During the study, the control eye of each animal was symptom-free.

The general state and behaviour of animals were normal throughout the study period. There were no notable body weight changes during the study period.

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

chemosis          : 0.00, 0.00, 0.00

discharge         : 0.00, 0.00, 0.00

redness             : 0.67, 0.67, 1.33

cornea opacity : 0.00, 0.00, 0.00

iris                    : 0.00, 0.00, 0.00

The test item Indium trihydroxide (In(OH)₃) (Batch No.: OH-1306), applied to rabbits’ eye mucosa, caused significant conjunctival effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 1 week.

According to Regulation (EC) No 1272/2008, Indium trihydroxide (In(OH)₃) does not require classification as an eye irritant.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

The in vitro skin corrosion test in the EPISKIN model with Indium trihydroxide (In(OH)3) (Kiss, CiToxLAB Hungary 2012) indicate that the test item is not a skin corrosive

An acute skin irritation study was performed with Indium trihydroxide in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the Draize method (OECD No.: 404, 2002) indicating that the test item is not a skin irritant

Eye irritation:

The in vitro eye irritation study in the Isolated Chicken Eyes model with indium trihydroxide (Kiss, CiToxLAB Hungary 2012) suggest that the test item is not irritating. According to the guideline OECD 438, indium trihydroxide does not require a classification as a severe eye irritant.

An acute eye irritation study of Indium trihydroxide (In(OH)3) performed in New Zealand White rabbits (Török-Bathó, CiToxLAB Hungary 2012). The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002). Indium trihydroxide (In(OH)₃), applied to rabbits’ eye mucosa, caused significant conjunctival effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 1 week.

Justification for classification or non-classification

Based upon OECD 431 in vitro skin corrosion data and OECD 404 in vivo skin irritation data, indium trihydroxide does not require classification as a skin irritant

Based upon OECD 438 in vitro eye irritation data and OECD 405 in vivo eye irritation data, indium trihydroxide does not require classification as an eye irritant.