Bis(hydroxylammonium) sulphate

Endpoint summary

Description of key information

Skin irritation:
irritating (Rabbit, 20 h, occlussive)

Eye irritation:

- not irritating (3 studies in rabbit)

- irritating (1 study in rabbit)

Respiratory system
No data available.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

; [application time: 1, 5, 15 min and 20 h (OECD: 4 h); 2 animals used (OECD: 1-3); observation period 8 days (OECD: 14); skin changes recorded on working days; dose ~1 ml (OECD: 0.5 ml), additionally testing of the ear (not recomm. by the OECD guideline)

Principles of method if other than guideline:

Before OECD guideline 404 was established, skin irritation was tested using an internal BASF method. White Vienna rabbits were used. Usually, 2 animals were treated for 1, 5, 15 min and 20 h using occlusive conditions. An application site of 2.5 cm x 2.5 cm was covered with the liquid test substance. In addition, skin tissue from the ear was tested by wrapping the ear. These results from the ear, however, would not be taken into account for evaluation as they do not represent testing of the dorsal/lateral flank of the back. After the application time, the skin was washed with water which sometimes contained a mild detergent. The animals were observed for 8 days. Skin reaction was recorded after 1 h, 24 h, 48 h, 72 h, 96 h and after 7 and 8 days.

GLP compliance:

no

Remarks:

GLP was not compulsory at the time the study was conducted.

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: male 3.32 kg, female 2.86 kg

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: the untreated sites of the same animal served as control.

Amount / concentration applied:

The test substance (ca. 2 g), moistured with water and mixed to a paste (concentration: 80 %), was applied to a 2.5 cm x 2.5 cm patch

Duration of treatment / exposure:

1, 5, 15 min, 20 hours

Observation period:

The animals were observed following exposure for 8 days on working days. Skin changes were recorded after removal of the bandage after 1 hour as well as after 24 h, 48 h, and on day 6 and 8.

Number of animals:

3 animals, 2 males and 1 female (2 animals were used for the 20 h treatments and one animal was used for th 1 min, 5 min and 15 min treatments).

Details on study design:

The test substance, moistured with water and mixed to a paste, was applied to a 2.5 cm x 2.5 cm patch (~2 g) and placed on the clipped and intact skin of four white Vienna rabbits for 1 min, 5 min, 15 min and 20 h under occlusive conditions.
The right and the left flank of each animal was clipped and the test material was administered on both sites (on the left and on the right site each and each application was scored separately).
The test substance was removed on both sites by washing once. Skin reactions were recorded after 1 h, 24 h, 48 h, and on day 6 and 8. The application time used for assessment was 20 hours, the test material was applied on dorsal skin. The corresponding reading time points used for assessment were 24 and 48 hours after application. Dermal reactions were classified using a BASF-scoring system, which is convertible into the current OECD Draize scheme. For the evaluation, the BASF scores given in the raw data were converted to Draize scores.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48 h

Score:

2.5

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: scale was seen on day 6

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: scale was seen on day 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: 72 hour time point was not evaluated

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: 72 hour time point was not evalutated

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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: Meets generally accepted scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

; 50 mm3 (one sharp-edged spoon) of test material applied (OECD0.1 ml,< 100 mg); 2 animals were used (OECD: 1-3); the eyes were not washed out after 24 h (OECD: washing after 24 h); observation period was 3 days (OECD: 21); exam. using fluorescein

Principles of method if other than guideline:

BASF-Test:
Before OECD guideline 405 was established, eye irritation was tested using an internal method. White Vienna rabbits were used. Usually approximately 50 µl or one sharp-edged spoon in case of solids of the test substance were applied to the conjunctival sac of one eye of 2 animals. The non- or saline- treated eye served as control. In studies with solids, talcum powder was alternatively used as control. The animals were observed several times on the treatment day and up to 8 days afterwards, and findings were recorded on working days.
The eyes were not washed out after 24 h as specified in OECD Guideline 405, which could be critical for solids which thus remained on the cornea for several days, causing mechanical damage. Probably, this would have been less severe if it had been washed out after 1 day.

GLP compliance:

no

Remarks:

; GLP was not compulsory at the time the study was conducted.

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: animal 1: 2.22 kg; animal 2: 2.12 kg

Vehicle:

unchanged (no vehicle)

Controls:

other: the second eye of the same rabbit was treated with 50 mg talcum powder.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: one sharp-edged spoon of the test substance, undiluted; ca. 50 mg

Duration of treatment / exposure:

24 h; the substance was not washed out.

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2 males

Details on study design:

One sharp-edged spoon of the undiluted, solid test substance was applied to the right conjuntival sac of one male and one female Vienna White rabbit. The left eye, treated with talcum powder, served as a control. The substance was not washed out.
Ocular reactions were recorded after 10 min, 1, 3 and 24 hours, as well as 48 and 72 h after instillation using a BASF-scoring system, which is convertible into the current OECD Draize scheme. For the evaluation the BASF scores given in the raw data were converted to Draize scores. The reading time points used for assessment were 24, 48 and 72 hours after application.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Table 1: Scores for eye irritation effects in the treated eyes as well as in the control eyes

Reading time point	Animal 1, treated eye (right)
	Cornea	Iris	Conjunctivae redness	Conjunctivae chemosis	Additional findings
10 min	0	0	1	0
1 h	0	0	1	1
3 h	1	0	2	2
24 h	1	0	1	2
48 h	0	0	1	0
72 h	0	0	0	0
Reading time point	Animal 1, control eye (left)
	Cornea	Iris	Conjunctivae redness	Conjunctivae chemosis	Additional findings
10 min	0	0	1	0
1 h	0	0	1	0
3 h	0	0	1	0
24 h	0	0	1	0
48 h	0	0	0	0
72 h	0	0	0	0
Reading time point	Animal 2, treated eye (right)
	Cornea	Iris	Conjunctivae redness	Conjunctivae chemosis	Additional findings
10 min	0	0	1	0
1 h	0	0	1	1
3 h	0	0	1	2
24 h	1	0	1	1
48 h	0	0	1	0
72 h	0	0	0	0
6 d	0	0	0	0
8 d	0	0	0	0
Reading time point	Animal 2, control eye (left)
	Cornea	Iris	Conjunctivae redness	Conjunctivae chemosis	Additional findings
10 min	0	0	1	0	substance residues
1 h	0	0	1	0	substance residues
3 h	0	0	1	0	substance residues
24 h	0	0	1	0
48 h	0	0	0	0
72 h	0	0	0	0
6 d	0	0	0	0
8 d	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Human data:

Human experience with local irritation/corrosion caused by hydroxylammonium sulfate is mentioned in the literature but respective reports are not available. Pellerat and Chabeau reported clinical skin irritation tests using concentrations of 1 and 2% hydroxylamine (no details on method given) with 34 persons, who had not been contacted to the substance earlier, 41% of these persons showed positive results (no further details provided (Pellerat and Chabeau 1976, Val. 4).

Animal data:

There are valid in vivo animal data available for the assessment of the skin and eye irritation potential of hydroxylammonium sulfate.

Skin

A Draize test was performed with White Vienna rabbits. A 20-hour occlusive exposure to ca. 2 g of the test substance (moistured with water and mixed to a paste) produced mean scores for erythema of 2.5 for animal 1 (male) and 2.0 for animal 2 (female), regarding the readings after 24 h and 48 h. The mean scores for edema for all animals were 0. Scaling was seen in both animals on day 6. The effects observed were fully reversible at the end of the observation period on day 8. This study was considered the key study for assessment of the endpoint.

In a second report, two rabbits were exposed to test material, administered as a 40 % aqueous solution for 20 h under occlusive conditions. A spot-like redness was reported at 24 h reading time point, but without appropriate score in both animals, which was fully reversible after 48 h after application of the test material. The mean score for edema was 0 for all animals at any reading time point. Since no scoring was conducted, this data cannot be used for assessment.

In one further report of limited validity, irritating effects were seen. However, only one animal was tested and the results are only available in the form of an abstract. Therefore, this information is of limited relevance for assessment.

Eye

A Draize test was performed with twoWhite rabbits, comparable to OECD guideline 405. Eyes were left unwashed after application of one sharp-edged spoon (ca. 50 mg) of the undiluted, solid test substance and were observed for 8 days. The mean score for conjunctivae redness was 0.66 in both animals, but was reversible within 72 h. The score for cornea was 0.33 in both animals, but was reversible within 48 h. The score for chemosis was 0.33 or 0.66, but was reversible in both animals within 48 h. The iris score was 0 at any reading time point in the treated eyes.

No irritating effects were also observed in a second study, comparable to OECD guideline 405. Eyes of two rabbits were left unwashed after application of the test material and were observed for 72 hours. A score of 0.5 was obtained for conjunctivae redness in both animals, the effect was fully reversible within 48 hours. No irritating effects were seen for cornea, iris and chemosis at any relevant reading time point used for assessment.

Another report of limited validity is available, which shows irritating effects but is not sufficiently reported.

Justification for classification or non-classification

According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, Annex VI the classification is:

- Skin Irrit. 2 (H315)

- Eye Irrit. 2 (H319)