Hydroxylammonium nitrate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

No data.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted prior to the establishment of standardised guidelines.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

For the initial induction, guinea pigs were administered hydroxylammonium sulphate (5%, in water) via intradermal injection. At day 7, animals were administered a topical induction of 25% of the test substance in water followed by a challenge treatment of 10% of the test substance in water at dat 21. At day 55, rechallenge was conducted.

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

Induction
Intradermal injection: 5% concentration of hydroxylammonium sulphate in water
Topical induction: 25% of hydroxylamonium sulphate in water

Challenge
10% hydroxylammonium sulphate

Route:

other: Epicutaneous (occlusivity not stated)

Vehicle:

water

Concentration / amount:

Induction
Intradermal injection: 5% concentration of hydroxylammonium sulphate in water
Topical induction: 25% of hydroxylamonium sulphate in water

Challenge
10% hydroxylammonium sulphate

No. of animals per dose:

24 animals

Details on study design:

For the initial induction, guinea pigs were administered hydroxylammonium sulphate (5%, in water) via intradermal injection. At day 7, animals were administered a topical induction of 25% of the test substance in water followed by a challenge treatment of 10% of the test substance in water at dat 21. At day 55, rechallenge was conducted.

Challenge controls:

Control animals were administered only vehicle during the intradermal and topical induction. At the challenge, 10% of the test substance in water was administered.

Positive control substance(s):

not specified

Positive control results:

No data

Reading:

1st reading

Group:

test chemical

Dose level:

10%

No. with + reactions:

22

Total no. in group:

24

Clinical observations:

moderate to intense redness and swelling

Remarks on result:

other: Reading: 1st reading. Group: test group. Dose level: 10%. No with. + reactions: 22.0. Total no. in groups: 24.0. Clinical observations: moderate to intense redness and swelling.

Reading:

2nd reading

Hours after challenge:

55

Group:

test chemical

Dose level:

10%

No. with + reactions:

22

Total no. in group:

24

Clinical observations:

moderate to intense redness and swelling

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 55.0. Group: test group. Dose level: 10%. No with. + reactions: 22.0. Total no. in groups: 24.0. Clinical observations: moderate to intense redness and swelling.

Reading:

1st reading

Group:

negative control

Dose level:

10%

No. with + reactions:

0

Total no. in group:

24

Clinical observations:

No dermal reactions were observed

Remarks on result:

other: Reading: 1st reading. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 24.0. Clinical observations: No dermal reactions were observed.

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Bis(hydroxylammonium)sulphate was shown to cause sensitisation reactions in guinea pigs.

Executive summary:

In Magnusson Kligman Test, similar to OECD Guideline 406, bis(hydroxylammonium)sulphate was administered to guinea pigs via intradermal injection on day 1 and topical application on day 7 as part of the induction period. Animals were challenged with the chemical on days 21 and 55 which caused sensitisation in 96% of the animals. Dermal reactions were classified into grade 2/3 (moderate to intense redness and swelling). By this study design in guinea pigs bis(hyroxylammonium)sulphate is considered to be a sensitising agent. This study is considered to be reliable with restrictions as the study was conducted prior to the establishment of standardised guidelines.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

One study did not identify hydroxylammonium sulphate as a dermal sensitiser, however the authors state that the study method was not sensitive to mild and moderate contact sensitisers. Therefore the result from the study may not be reliable and could have indicated a false negative for the test chemical. This study was therefore discounted. A further two studies were located that both concluded that hydroxylammonium sulphate caused sensitisation reactions in mice and guinea pigs respectively.

Migrated from Short description of key information:
Hydroxylammonium sulphate, an analogue of hydroxylammonium nitrate, is considered to be a dermal sensitiser based on results in guinea pigs and mice.

Justification for selection of skin sensitisation endpoint:
Of the three studies located, this study is most consistent with standardised guidelines.

Respiratory sensitisation

Link to relevant study records

Reference

Endpoint:

respiratory sensitisation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study not conducted to GLP or standardised guidelines, however it remains well reported and of adequate design for its purpose

Principles of method if other than guideline:

Guinea pigs were administered hydroxylammonium sulphate via intradermal injection (5% in water) on day 1 and topical application on day 7 (10% in water). Animals were initially challenged by topical application (10% in water) on day 21. Animals were rechallenged with the test chemical via inhalation at doses of 0.0065 or 0.0132 mg/l for 30 minutes or via the intratracheal route at doses of either 5, 15, 25 and 75 mg/kg. Breathing rates were measured during exposure and 60 minutes after exposure.

GLP compliance:

not specified

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Route of induction exposure:

other: Intradermal and topical

Route of challenge exposure:

other: Inhalation and intratracheal

Vehicle:

not specified

Concentration:

Inhalation: 0.0065 mg/l and 0.0132 mg/l
Intratracheal: 5, 15, 25 and 75 mg/kg

No. of animals per dose:

4

Details on study design:

Guinea pigs were administered hydroxylammonium sulphate via intradermal injection (5% in water) on day 1 and topical application on day 7 (10% in water). Animals were initially challenged by topical application (10% in water) on day 21. Animals were rechallenged with the test chemical via inhalation at doses of 0.0065 or 0.0132 mg/l for 30 minutes or via the intracheal route at doses of either 5, 15, 25 and 75 mg/kg. Breathing rates were measured during exposure and 60 minutes after exposure.

Challenge controls:

No data

Results:

There was no increase in breathing rates during either the administration period or 60 minutes after the exposure. The authors considered an alteration in breathing rates as an indication of pulmonary sensitisation.

Positive control results:

No data

Negative control results:

no data

Interpretation of results:

not sensitising

Conclusions:

Hydroxylammonium sulphate did not cause respiratory tract irritation in guinea pigs after induction via intradermal and topical application.

Executive summary:

In a respiratory tract sensitisation study, guinea pigs were administered hydroxylammonium sulphate via intradermal (5% in water) and topical application (10% in water) on day 1 and 7, respectively, as part of the induction process. Animals were initially challenged by topical application (10% in water) on day 21. Animals were rechallenged with the test chemical via inhalation at doses of 0.0065 or 0.0132 mg/l for 30 minutes or via the intracheal route at doses of either 5, 15, 25 and 75 mg/kg. Breathing rates remained unchanged during the treatment period and for 60 minutes after the exposure which the authors considered to a be an indication that no pulmonary sensitisation had occurred. Hydroxylammonium sulphate was therefore considered to not cause respiratory tract sensitisation in guinea pigs by this study design.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Hydroxylammonium sulphate, an analogue of hydroxylammonium nitrate, did not cause respiratory tract sensitisation in guinea pigs after induction via intradermal and topical application. However, only one study was located based in one species in a none-standardised guideline, therefore the results should be interpreted with caution.

Migrated from Short description of key information:
Hydroxylammonium) sulphate, an analogue of hydroxylammonium nitrate, did not cause respiratory tract sensitisation in guinea pigs after induction via intradermal and topical application. However only one study was located based in one species in a none-standardised guideline, therefore results should be interpreted with caution.

Justification for selection of respiratory sensitisation endpoint:
Only one respiratory sensitisation study was located.

Justification for classification or non-classification

Hydroxylammonium nitrate is classified as Skin Sens 1.