Registration Dossier

Administrative data

Description of key information

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:
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 group
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 group
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 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.