Hydroxylammonium chloride

Endpoint summary

Description of key information

Acute toxicity, oral (similar to OECD 401, RL2), male and female rats: LD50 = 642 mg/kg bw

RA from source substance bis(hydroxyammonium) sulfate (CAS 10039-54-0)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

642 mg/kg bw

Interpretation of results:

other: Category 4 based on CLP/EU GHS criteria, according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Acute Oral 4, H302 (Annex VI harmonized classification)

The available data on acute toxicity (oral) are in consistency with the harmonized classification according to Regulation (EC) 1272/2008, Annex VI.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

642 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (RL2) from a reference substance with similar structure. Read-across is justified based on structural similarities and similar chemical behaviour. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other:

Remarks:

Meets generally accepted scientific principles. But route of application (subcutaneous) is not in line with international guidelines and therefore not acceptable for the assessment of acute dermal toxicity. The present study may only be used as worst case assessment and support for the waiving argumentation.

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Test item was applied subcutaneously
- Parameters analysed / observed: LD 50

GLP compliance:

not specified

Test type:

standard acute method

Species:

mouse

Strain:

other: Agnes-Blum

Sex:

female

Type of coverage:

other: subcutaneous application

Vehicle:

not specified

Duration of exposure:

24 h

Doses:

3 different doses

No. of animals per sex per dose:

10 females

Control animals:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

125.08 mg/kg bw

Based on:

test mat.

Remarks on result:

other: effect level calculated from 1.8 mMol/kg bw

Interpretation of results:

other: Category 4 based on CLP/EU GHS criteria, according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Acute Dermal 4, H312 (Annex VI harmonized classification)

The subcutaneous application of the test substance can be considered as worst case demonstrating the hazardous potential of hydroxylammonium chloride which is in line with the harmonized classification.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

In accordance with Column 2 of Annex VIII, Section 8.5, of Regulation (EC) No 1907/2006, in addition to the oral route (Annex VII, 8.5.1.), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. Since inhalation of the substance is unlikely with regard to the particle size, testing by the dermal route is appropriate.
Supporting information comprises a study with the target substance using subcutaneous application of the test substance, which can be considered as worst case demonstrating the hazardous potential of hydroxyl ammonium chloride which is in line with the harmonized classification as Acute Tox 4 dermal, H312 according to Annex VI of the CLP Regulation (EC) 1272/2008.

Additional information

Justification for read-across

No data on acute toxicity after oral administration are available for the target substance hydroxylammonium chloride (CAS 5470-11-1). Therefore, read across from the relevant source substance bis(hydroxyammonium) sulfate (CAS 10039-54-0) was applied to obtain information regarding acute toxicity after oral exposure.

Read-across from an appropriate reference substance is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.5. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

There is supporting data available regarding acute dermal toxicity for Hydroxylammonium chloride (CAS 5470-11-1).

Acute oral toxicity

CAS 10039-54-0

An acute oral toxicity study was performed with the test substance similar to OECD guideline 401 (reference 7.2.1-1). Groups of 10 male and 10 female rats received oral gavage doses of 200 - 1600 mg/kg bw. The animals were observed for 7 days after administration. The following mortalities were recorded: 0/20, 1/20, 6/20, 13/20, 10/20, 15/20, 18/20 and 20/20 at 200, 400, 500, 640, 800, 1000, 1250 and 1600 mg/kg bw, respectively. Clinical signs comprised intermittent breath and dyspnoe, apathy, cynosis, agitated behaviour, stretching, and slight tremor at a dose range of 400 – 800 mg/kg bw immediately after application of the test substance. Some of the surviving animals had unkempt fur and intermittent breath on the next day. Similar effects were seen at a dose range of 1000 – 1600 mg/kg bw shortly after application of the test substance, some of which persisted until the next day. Necropsy revealed a dark blue to violet or black discolouration and enlargement of the spleen. The rest of the animals showed no abnormal gross findings in the examined organs and tissues. The acute oral LD50 was 642 mg/kg bw.

The analogue substance Bis (hydroxyammonium) sulfate (CAS 10039-54-0) meets the criteria for classification as Acute Tox. 4, H302, according to Regulation (EC) 1272/2008 based on the reported findings on acute oral toxicity.

Acute dermal toxicity

CAS 5470-11-1

Supporting information is available on an acute dermal toxicity study performed with the test substance (Oehme et al., 1968). 10 female Agnes-Blum mice were injected with three different doses of the test substance for 24 h. No further information is available. The acute dermal LD50 in mice was found to be 125.08 mg/kg bw after subcutaneous application.

The subcutaneous application of the test substance can be considered as worst case demonstrating the hazardous potential of hydroxyl ammonium chloride which is in line with the harmonized classification as Acute Tox 4 dermal, H312 according to Annex VI of the CLP Regulation (EC) 1272/2008.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Hydroxylammonium chloride, data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Applying the RA-A approach and in consistency with the harmonized classification, which is available for the target and the source substance bis(hydroxyammonium) sulfate (CAS 10039-54-0) according to Regulation (EC) 1272/2008, Annex VI (both with the Index No. 612-123-00-2), the target substance Hydroxylammonium chloride meets the criteria for classification as Acute oral Tox. Cat. 4, H302 and Acute dermal Tox. Cat. 4, H312.