Hydroxylamine

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Additional information:

For hydroxylamine (free base) no data is available. However, valid studies of the corresponding salts "hydroxylamine sulfate" and "hydroxylamine chloride" are available:

CAS No. 10039-54-0:

Skin sensitization:

There is information available to assess 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 (Gad, 1986, according to OECD 406). 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 (Griffith, 1977, according to OECD 406) 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.

Hydroxylammonium sulphate (40 % in water) was applied to one side of the flanks of 10 guinea pigs (skin painting test, BASF AG, 1956). 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 (Gad, 1986) prior to the first induction treatment mice (10-15 animals) received two i.d. injections (overall 0.05 ml) FCA into the stomach region. 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 by Gad, 1986 was used by two other laboratories (Dunn, 1990). However, both laboratories reported negative results with hydroxylammonium sulphate.

There are two additional tests with limited validity that show a sensitizing potential of hydroxylammonium sulphate (Allied Corporation, 1984: only secondary literature, cited in the EU Risk Assessment Report of bis(hydroxylammonium)sulphate; TSCAT 88-920008864: only a short note available). 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 (, 1977). There are also two case reports (Val. 4; Goh, 1990: only short communication available; Pellerat, 1976: original reference not translated, written in french) which also describe a sensitizing potential of hydroxylammonium sulphate.

CAS No. 5470-11-1:

Skin sensitization:

There are no in vivo data, but human case reports available concerning the skin sensitizing potential of hydroylammonium chloride. Folesky (1971) described 7 cases of dermatitis among 20 chemicants involved in the production of hydroxylammonium chloride. Patch testing with 0.1 and 1 % hydroxylammonium chloride solutions gave unequivocally positive responses at the low dose level within 24 to 48 h. There are two other case reports (Val. 4; Gobbi, 1979: original reference not translated (written in Italian), only a short English summary available, Aguirre, 1992: only short communication) describing workers (involved in the production of cycloserine) and a photographer, respectively, with dermatitis. Hydroxylamine hydrochloride was suspected as causing agent. In both cases patch tests with aqueous hydroxylammonium chloride solutions (0.1 % or 1 %) confirmed a sensitising potential of hydroxylammonium chloride.

Migrated from Short description of key information:
For hydroxylamine (free base) no data is available. However, valid studies of the corresponding salts "hydroxylamine sulfate" and "hydroxylamine chloride" are available:

CAS No. 10039-54-0:
Guinea pig maximisation test: skin sensitizing (acc. OECD 406, Gad, 1986)
Buehler test, guinea pig: not skin sensitizing (acc. OECD 406, Griffith, 1977)
Skin painting test, guinea pig: skin sensitizing (BASF AG, 1956)
Mouse ear swelling test: skin sensitizing (Gad, 1986)
Mouse ear swelling test: not skin sensitizing (Dunn, 1990)
Patch test with volunteers: skin sensitizing (Griffith, 1977)

CAS No. 5470-11-1:
No animal data available.
Human case report: sensitizing (Folesky, 1971)

Respiratory sensitisation

Endpoint conclusion

Additional information:

CAS No. 10039-54-0:

Respiratory sensitization:

One report concerning respiratory sensitization of bis(hydroxylammonium) sulphate is available (Allied Corporation, 1984; Val. 4: only secondary literature, cited in the EU Risk Assessment Report of bis(hydroxylammonium)sulphate, CAS No. 10039-54-0). 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 in sensory irritation).

 

CAS No. 5470-11-1:

Respiratory Sensitization:

No information available.

 

CAS No. 7803-49-8:

Respiratory Sensitization:

No information available.

Migrated from Short description of key information:
CAS No. 10039-54-0:
Guinea pig maximisation test with an inhalation aerosol or intratracheal challenge: not respiratory sensitizing (Allied Corporation, 1984, Val. 4)

CAS No. 5470-11-1:
No information available.

CAS No. 7803-49-8:
No information available.

Justification for classification or non-classification

CAS No. 10039-54-0:

Due to the positive animal experiments skin sensitizing properties of the test substance were demonstrated. This correlates with human data and therefore labeling as Xi, R43 (may cause sensitization by skin contact) according to EU and as "Category 1" according to GHS criteria is appropriate.

There is no indication given that bis(hydroxylammonium) sulphate is a sensitizer of the respiratory tract.

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

Skin Sens. 1