Aluminium metaphosphate

Endpoint summary

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP)
Eye irritation: not irritating (OECD 405, GLP)
Respiratory irritation: no study available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion, other

Remarks:

Study for skin irritation in vivo has been performed prior to the 2016 update of the REACH Regulation.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Jul - 05 Aug 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Zika

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kaninchenbetrieb Kock, Warnkenhagen, Germany
- Age at study initiation: reported as young adults
- Weight at study initiation: 3.13-4.85 kg
- Housing: single-caged
- Diet: conventional laboratory diet (a half-and-half blend of “Holzenstolz Kaninchenverbrauchsfutter 2, Type 038” [Wilhelm Stroeh jr. GmbH & Co. KG, Germany] and “Rabbit maintenance, MuesliMash” [ssniff Spezialdiäten GmbH, Germany]), ad libitum
- Water: tap water (drinking quality), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

moistened with 500 µL water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 h

Observation period:

4 days
Reading time points: 1, 24, 48 and 72 h after patch removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: ca. 6 cm²
- Type of wrap if used: semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of the exposure period with water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of all 3 animals

Time point:

other: mean from gradings at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all 3 animals

Time point:

other: mean from gradings at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

Immediately after patch removal (one animal only): no skin reactions were observed.
1-72 h: no skin reactions were observed in any animal at any obervation time point.

Other effects:

No further local or systemic effects were observed.
There were no effects in body weight development.

Table 1. Summary of skin reactions

Skin reaction	Grading time point (after patch removal)	Individual scores – Rabbit number and sex
		2013-17 female	2013-18 female	2013-26 female
Erythema	Immediately	0	-	-
	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
Mean score from gradings at 24, 48 and 72 h		0	0	0
Edema	Immediately	0	-	-
	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
Mean score from gradings at 24, 48 and 72 h		0	0	0

 

Table 2. Summary of body weight (gain)

Rabbit number and sex	Individual body weight (kg)		Body weight change (kg)
	Day 0	Day 4
2013-17 female	3.54	3.59	+0.05
2013-18 female	4.85	4.89	+0.04
2013-26 female	3.13	3.21	+0.08

 

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the test material caused no skin irritating/corrosive reactions. The individual mean values for erythema/eschar and edema from gradings at 24, 48 and 72 h were 0 in all three animals. Therefore, the material does not fulfil the criteria for classification according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), and is thus considered to be not skin irritating.

CLP: not classified
GHS: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation, other

Remarks:

Study for skin irritation in vivo has been performed prior to the 2016 update of the REACH Regulation.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 May - 24 Jun 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Zika

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kaninchenbetrieb Kock, Warnkenhagen, Germany
- Age at study initiation: 16-20 weeks
- Weight at study initiation: 3.30-4.43 kg
- Housing: single-caged
- Diet: conventional laboratory diet (a half-and-half blend of “Holzenstolz Kaninchenverbrauchsfutter 2, Type 038” [Wilhelm Stroeh jr. GmbH & Co. KG, Germany] and “Rabbit maintenance, MuesliMash” [ssniff Spezialdiäten GmbH, Germany]), ad libitum
- Water: tap water (drinking quality), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

1 h

Observation period (in vivo):

5 days (2 animals) and 14 days (one animal)
Reading time points: 1, 24, 48, 72 and 96 h post-instillation

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The solid test substance had not been removed from the eyes of the test animals by physiological mechanisms at the first observation time point, therefore the treated eyes were rinsed with physiological saline.
- Time after start of exposure: 1 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: slit lamp biomicroscope / fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 3 animals

Time point:

other: mean from gradings at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 3 animals

Time point:

other: mean from gradings at 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean from gradings at 24, 48 and 72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 96 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean from gradings at 24, 48 and 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 96 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean from gradings at 24, 48 and 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 96 h

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all 3 animals

Time point:

other: mean from gradings at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

1 h post-instillation: slight corneal opacity in 1/3 animals, no effects on iris, moderate conjunctival redness in 3/3 animals, slight chemosis in 3/3 animals
24 h: no corneal opacity, iritis or chemosis, slight and moderate conjunctival redness in 2 and 1 animals, respectively.
48 h: slight conjunctival redness in 3/3 animals
72 h: slight conjunctival redness in 3/3 animals
96 h: no ocular effects observed in any animal

Other effects:

No further local or systemic effects were observed.
There were no effects in body weight development.

Table 1. Summary of eye reactions

Eye reaction	Grading time point (after instillation)	Individual scores – Rabbit number and sex
		2013-16 female	2013-17 female	2013-18 female
Cornea	1 h	0	0	1
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	96 h	0	0	0
Mean score from gradings at 24, 48 and 72 h		0	0	0
Iris	1 h	0	-	-
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	96 h	0	0	0
Mean score from gradings at 24, 48 and 72 h		0	0	0
Conjunctivae	1 h	2	2	2
	24 h	2	1	1
	48 h	1	1	1
	72 h	1	1	1
	96 h	0	0	0
Mean score from gradings at 24, 48 and 72 h		1.3	1	1
Chemosis	1 h	1	1	1
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	96 h	0	0	0
Mean score from gradings at 24, 48 and 72 h		0	0	0

 

Table 2. Summary of body weight (gain)

Rabbit number and sex	Individual body weight (kg)		Body weight change (kg)
	Day 0	Day 5 or 14*
2013-17 female	3.30	3.53	+0.23
2013-18 female	4.43	4.83	+0.40
2013-26 female	4.16	4.61	+0.45

*Animal 2013-16 (initial test) was observed for 14 days, animals 2013-17 and 2013-18 (confirmatory test) were observed for 5 days post-instillation.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the test material caused no eye irritating/corrosive reactions. The individual mean values from gradings at 24, 48 and 72 h were 0 for corneal opacity, iritis and chemosis in all 3 animals, and 1.3/1.0/1.0 for conjunctival redness in each animal. The observed effects were fully reversible within 96 h post-instillation. Therefore, the material does not fulfil the criteria for classification according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), and is thus considered to be not eye irritating.

CLP: not classified
GHS: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Aluminium metaphosphate was tested for induction of skin irritation in rabbits (strain: Zika) according to OECD Guideline 404 and in compliance with GLP (Prietzsch, 2014). The test animals (1 in the initial test, 2 in the confirmatory test) were dermally exposed to 0.5 g of the test material (moistened with 500 µL water) for 4 h. Skin reactions were evaluated immediately (first animal), 1, 24, 48 and 72 h after patch removal. No skin reactions were observed in any animal at any reading time point. The study was therefore terminated on Day 4. No further local or systemic effects were noted and there were no abnormalities in body weight development. The individual mean values for erythema/eschar and edema from gradings at 24, 48 and 72 h were 0 in all three animals.

Therefore, the test material does not fulfil the criteria for classification according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), and is thus considered to be not skin irritating.

Eye irritation

The eye irritating potential of aluminium metaphosphate was evaluated in rabbits (strain: Zika) in a GLP-study performed in accordance with OECD Guideline 405 (Prietzsch, 2014). The test material (100 mg) was applied into the conjunctival sac of one eye of each animal, the other eye serving as control. The test material (solid powder) was removed from the treated eyes at 1 h post-instillation by rinsing with physiological saline. Ocular reactions were examined and scored at 1, 24, 48, 72 and 96 h post-instillation. No effects on the iris were observed in any animal at any time point. At the 1 h reading, slight corneal opacity was noted in 1 animal and slight chemosis in all 3 animals, which had both fully reversed at the 24 h reading. Moderate conjunctival redness was observed in all animals at the 1 h reading. Conjunctival redness decreased to slight but persisted in all animals up to the 72 h reading. At 96 h post-instillation, all treated eyes had fully reversed to normal. No further local or systemic effects were noted and there were no abnormalities in body weight development up to the end of the observation period (14 days for the animal in the initial test, 5 days for the 2 animals in the confirmatory test). The individual mean values from gradings at 24, 48 and 72 h were 0 for corneal opacity, iritis and chemosis in all 3 animals, and 1.3/1.0/1.0 for conjunctival redness in each animal, respectively. The observed effects were fully reversible within 96 h post-instillation.

Therefore, the test material does not fulfil the criteria for classification according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), and is thus considered to be not eye irritating.

Justification for classification or non-classification

The available data indicate that the substance does not meet the classification criteria in accordance with Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

CLP

Skin irritation/corrosion: not classified

Eye irritation: not classified

Respiratory irritation: data lacking

GHS

Skin irritation/corrosion: not classified

Eye irritation: not classified

Respiratory irritation: data lacking