Methoxyammonium chloride

Endpoint summary

Description of key information

No reliable data are available for the test substance. The toxicological assessment is based on read-across to CAS 10039-54-0 (skin irritation) and CAS 5470-11-1 (eye irritation)

Irritation:
- skin: mild irritant (according to CLP Regulation); rabbit 20h, occlusive (Draize test similar to OECD TG 404, non-GLP, reliability 2)
- eye: corrosive; rabbit (similar to OECD TG 405, non-GLP, reliability 2)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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 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:

2 animals for each application times:
1 male and 1 female for the application time 20 h; 2 males for an application of 1, 5 and 15 minutes

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 internal scoring system, which is convertible into the current OECD Draize scheme.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 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:

other: 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:

other: 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:

other: 24-48 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: 72 hour time point was not evaluated

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Under the experimental conditions chosen the mean scores for erythema after an application time of 20 hours under occlusive conditions indicate a mild irritating potential of the test substance.

Executive summary:

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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); 4 animals were used (OECD: 3); the eyes were not washed out after 24 h (OECD: washing after 24 h); observation period was 8 days (OECD: 21)

Principles of method if other than guideline:

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: 3.11 kg; animal 2: 2.7 kg; animal 3: 3.34 kg; animal 4: 2.92 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 and 2 females

Details on study design:

One sharp-edged spoon (ca. 50 mg) 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 withtalcum powder, served as a control. The substance was not washed out.
Ocular reactions were recorded after 10 min, 1, 3, 24, 48 and 72 hours, as well as 6 and 8 days after instillation in 2/4 animals or alternatively after 10 min, 1, 3, 24 and 48 hours, as well as 5, 6 and 9 days after instillation in the remaining two animals 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 (animal 1 and 3) and 24, 48 hours after application (animal 2 and 4), respectively.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24-48-72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: see table for details

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24-48 h

Score:

2.5

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: see table for details

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24-48-72 h

Score:

2.33

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: see table for details

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

other: 24-48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24-48-72 h

Score:

0.66

Max. score:

2

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: see table for details

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24-48 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24-48-72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

animal #4

Time point:

other: 24-48 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24-48-72 h

Score:

0

Max. score:

3

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24-48 h

Score:

0

Max. score:

3

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24-48-72 h

Score:

0

Max. score:

3

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

other: 24-48 h

Score:

1.5

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24-48-72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: see table for details

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24-48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24-48-72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: see table for details

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

other: 24-48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The test item causes serious eye damage/irritation.

Executive summary:

Before OECD guideline 405 was established, eye irritation was tested using an internal method. White Vienna rabbits were used. The test substance was applied to the conjunctival sac of one eye of 2 animals. The non- or saline- treated eye served as control.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. 

Severe eye irritation effects were seen in the treated eyes of the animals, including the occurence of staphyloma in two cases. The effects observed were in some cases not fully reversible at the end of the observation period after 8 days.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No reliable data for the test substance do exist. The toxicological assessment is based on the available data of CAS 10039-54-0 (skin irritation) and CAS 5470-11-1 (eye irritation).

 

Skin:

A Draize test (similar to OECD 404, non-GLP, reliability 2) 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. Under the experimental conditions chosen the mean scores for erythema after an application time of 20 hours under occlusive conditions indicate a mild irritating potential of the test substance.

 

Eye:

Before OECD guideline 405 was established, eye irritation was tested using an internal method. White Vienna rabbits were used. The test substance was applied to the conjunctival sac of one eye of 2 animals. The non- or saline- treated eye served as control.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. Severe eye irritation effects were seen in the treated eyes of the animals, including the occurence of staphyloma in two cases. The effects observed were in some cases not fully reversible at the end of the observation period after 8 days.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. In a reliable rabbit study the erythema scores for the test item treated tissues indicate the classification as mild skin irritant Cat.3. 
The available data for eye irritation lead to a classification severe eye damage Cat. 1 (H318) under Regulation (EC) No. 1272/2008, as amended for the seventeenth time in Regulation (EC) No. 2021/849.