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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

Oral, rat (OECD 414, GLP): NOAEL (maternal) = 3 mg/kg bw/d, NOAEL (developmental toxicity) ≥ 20 mg/kg bw/d

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

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
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
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
3 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: no treatment-related adverse effects on dams observed
Remarks on result:
other: Source: 7.8.2-1
Key result
Dose descriptor:
LOAEL
Remarks:
systemic
Effect level:
10 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
organ weights and organ / body weight ratios
Remarks on result:
other: Source: 7.8.2-1
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
5 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
haematology
organ weights and organ / body weight ratios
Remarks on result:
other: Source: 7.8.2-2
Key result
Dose descriptor:
LOAEL
Remarks:
systemic
Effect level:
15 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
gross pathology
haematology
organ weights and organ / body weight ratios
Remarks on result:
other: Source: 7.8.2-2
Key result
Abnormalities:
no effects observed
Key result
Dose descriptor:
NOAEL
Remarks:
developmental toxicity
Effect level:
> 20 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects on the fetuses occured at the highest tested dose level of 20 mg/kg bw.
Remarks on result:
other: Source: 7.8.2-1
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
Based on the analogue approach, no adverse effects on developmental toxicity are considered for hydroxylammonium chloride. The NOAEL systemic was considered to be 3 mg/kg bw/day in dams and the NOAEL for developmental toxicity was considered to be > 50 mg/kg bw/day in the offspring.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable and consistent studies, 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-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Justification for read-across

There are no data regarding reproductive toxicity available for hydroxylammonium chloride (CAS 5470-11-1). In order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.7, read-across from an appropriate substance is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. 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).

As no data is available regarding reproductive toxicity for hydroxylammonium chloride (CAS 5470-11-1) information from the analogue substance bis(hydroxylammonium)sulfate (CAS 10039-54-0) are taken into account to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.7.

CAS 10039-54-0

A pre-screen test on developmental toxicity of bis(hydroxylammonium)sulfate (CAS 10039-54-0) was investigated according to OECD Guideline 414 (prenatal developmental toxicity study) and GLP (reference 7.8.2-2). Groups of 10 presumed pregnant female Wistar rats received daily oral gavage doses of the test substance at 5, 15 and 30 mg / kg bw/day during gestational days 6 to 15. Control animals were treated with the concurrent vehicle. On day 16 of gestation the animals were euthanized and examined for maternal and fetal parameters. Maternal toxicity such as severe haemolytic anemia, significant increase of absolute and relative spleen weights and a considerable enlargement of the spleen were observed in mid- and high-dose females. Based on these results in maternal animals the NOAEL for maternal toxicity was found to be 5 mg/kg bw/day. Examination of fetus litter size and weights, offspring viability (number alive and number dead) and grossly visible abnormalities revealed no differences to controls and thus no indication for effects on developmental toxicity. A NOAEL for developmental toxicity was not derived, since the examination of the uterus content was very limited due to the stage of development of the implants on the day when the study was terminated (Day 16 p.c.).

Based on the results of the pre-screen test, a second developmental toxicity test with bis(hydroxylammonium)sulfate (CAS 10039-54-0) was investigated according to OECD Guideline 414 (prenatal developmental toxicity study) and under GLP conditions (reference 7.8.2-1). Untreated male Wistar rats were mated with untreated female Wistar rats, which then received daily oral gavage doses of the test substance at concentrations of 1, 3, 10 and 20 mg/kg bw/day during gestational days 6 to 15. 25 females per treatment group were used. Control animals received the vehicle Milli-Q-water. On day 20 post coitum the animals were sacrificed and examined for maternal and fetal parameters. The test substance caused some overt signs of maternal toxicity at 10 and 20 mg/kg bw/d, while 1 or 3 mg/kg bw/d were tolerated by the dams without any substance-induced findings. At the dose levels of 10 and 20 mg/kg bw/d a significant enlargement of the spleen was observed, which was a consequence of a severe haemolytic anemic process already demonstrated in the pre-screen test on developmental toxicity (reference 7.8.2-2). The gestational parameters were not influenced by the test substance. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 3 mg/kg bw/day. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, soft tissue and skeletal abnormalities revealed no adverse effects in any treatment groups compared with the control animals. The NOAEL for developmental toxicity in rats for bis(hydroxylammonium)sulfate (CAS 10039-54-0) was found to be ≥ 20 mg/kg bw/day.

 

Conclusion for developmental toxicity

The available data show that the analogue substance bis(hydroxylammonium)sulfate (CAS 10039-54-0) does not show intrinsic hazardous properties with regard to developmental toxicity. Therefore, based on common functional groups and structural similarities, hydroxylammonium chloride (CAS 5470-11-1) is not expected to exhibit developmental toxicity/teratogenicity.

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.

The available data on developmental toxicity from the source substance bis(hydroxylammonium)sulfate (CAS 10039-54-0) do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.

Therefore, applying the RA-A approach, the target substance is also considered not to meet the classification criteria for developmental toxicity according to Regulation (EC) No 1272/2008

Additional information