Bis(hydroxylammonium) sulphate

Endpoint summary

Description of key information

Skin sensitization:

GPMT: sensitizing

Skin paining test: sensitizing

MEST: sensitizing (additional tests: not sensitizing)

Patch test (human): sensitizing

Respiratory sensitization:

Guinea pig maximisation test with an inhalation aerosol or intratracheal challenge: not respiratory sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication (with a short method description) which meets basic scientific principles.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

not applicable

Remarks:

(due to missing details in the method description)

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study was performed prior to existence of LLNA guideline.

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Acclimation period: 14 days

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

- intradermal injection: 5%; - topical induction: 25%

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

- challenge: 10%

No. of animals per dose:

15 (test group), 6 (control group)

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- Exposure period: 48 h
- Site: intradermal injected skin site


B. CHALLENGE EXPOSURE
- Exposure period: 24 h
- Site: naive skin site

Group:

test chemical

No. with + reactions:

15

Total no. in group:

15

Remarks on result:

positive indication of skin sensitisation

100% of the treated guinea pigs showed a positive reaction. Based on a self-made ranking and classification system (Gad,1988), hydroxylamine sulfate has to be classified in class III (moderate sensitizer).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Several studies are available regarding the skin sensitization potential of bis-(hydroxylammonium) sulphate.

An in vivo study with 15 guinea pigs in the test group and 6 guinea pigs as control group was conducted, according to the method described by Magnusson and Kligman. Intradermal injection was conducted with the test material (5 %) in water, FCA and the test material 5 % in FCA. Epicutaneous induction (one week after intradermal induction) was conducted with 25 % of the test material in water. The challenge (14 days after epicutaneous induction) was performed with 10 % of the test material in water. 100% of the treated guinea pigs showed a positive reaction, therefore the test result was considered as positive.

A Buehler test with 20 guinea pigs in the treatment group (an equal number of previously untreated animals was challenged as a control and a third group (unknown number of animals) was carried through the entire test as a vehicle control). The test compound (0.2 % in surfactant solution) was applied to the skin for a 6 h treatment period once each week for 3 successive weeks. This induction series was followed in 2 weeks by dual 6 h challenge patches on the depilated flanks of each animal (test substance concentration: 0.2% in surfactant solution). 0/20 treated animals showed a positive result.

In a non-guideline skin paining test, test substance (40 % in water) was applied to one side of the flanks of 10 guinea pigs. This procedure was repeated daily until irritation was clearly observed. 12 days after the last induction procedure the other flank of the animals was treated with 4 % aqueous hydroxylammonium sulphate solution. At this site 8/10 animals showed irritation, edema and little nodules demonstrating a sensitizing effect.

In a mouse ear swelling test, mice (10-15 animals) received two i.d. injections (overall 0.05 ml) FCA into the stomach region prior to the first induction treatment. Then, the animals were topically dosed at the stomach site with 10 % hydroxylammmonium sulphate in 25 % ethanol at three consecutive days. After a rest period of 7 days 10 % of the test compound in 25 % ethanol was applied to the right ear. The control group consisted of 5 – 10 mice. A total of 72 compounds were tested. 33 % of the mice treated with hydroxylammonium sulphate showed a positive reaction. The identical test procedure (mouse ear swelling test) described was used by two other laboratories. However, both laboratories reported negative results with hydroxylammonium sulphate.

Additional tests support the assessment of the test substance as sensitizing, however, only abstracts are available for these studies.

Data of human subjects support the sensitizing property of hydroxylammonium sulphate. Hydroxylammonium sulphate sensitized 3 of 76 (4 %) human subjects in an epicutaneous patch test. The patches were left on the dorsal skin of the upper arm for 24 h and were applied 3 days per week for 3 weeks. At the beginning of the 6th week, each subject is challenged with the test material at the same sites as used for induction and at fresh sites on the opposite arm. The challenge patches are removed after 24 h. There are also two case reports of limited validity which also describe a sensitizing potential of hydroxylammonium sulphate.

Respiratory sensitisation

Endpoint conclusion

Additional information:

Respiratory sensitization:

One report concerning respiratory sensitization of bis(hydroxylammonium) sulphate is available (cited in the EU Risk Assessment Report of bis(hydroxylammonium)sulphate). Guinea pigs that have been subjected to a Magnusson Kligman Test with bis(hydroxylammonium) sulphate were subsequently treated as follows: 2 groups of 4 animals inhaled an aerosol (0.0065 mg/l and 0.0132 mg/l, respectively) for 30 min. Four other groups of guinea pigs (4/group) were treated via the intratracheal route (5, 15, 25 and 75 mg/kg bw). Based on measured changes in breathing rates from base line levels the substance did not produce any indication of pulmonary sensitization (an increase in breathing rates was considered a sign of pulmonary sensitization and a decrease in breathing rate a sign of sensory irritation).

Additionally, a case report on occupational asthma in two workers of the paper recycling industry is available. The authors correlate the onset of asthma with the introduction of hydroxylamine into the de-inking process and the subsequent exposure of both workers. However, the exposure is not described, confounding factors are not sufficiently addressed and the question whether other chemicals used in the process might be the cause of the symptoms is not addressed at all. Exposures to possible respiratory sensitizers in the non-work environment has not been excluded and no information is given on whether this was monitored during the described "occupational challenge" of Mr. Y. Therefore, the information reported cannot be used for assessment.

Justification for classification or non-classification

Skin sensitization:

Based on the data available and in accordance with the criteria laid down in Regulation EC 1272/2008 (CLP), classification for skin sensitizing properties is warranted. In accordance with the listing in Annex VI of Regulation 1272/2008, the substance is classified as H317 ("May cause an allergic skin reaction").

Respiratory sensitization:

Based on the data available and in accordance with the criteria laid down in Regulation EC 1272/2008 (CLP), conclusive human evidence or indicative animal studies must be available to assess the potential of a substance to cause respiratory sensitization. In this case, indicative animal data suggest the substance be a non-sensitizer and a poorly reported case study does not provide conclusive evidence to the contrary. Therefore, non-classification for respiratory sensitization is warranted.