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Administrative data

Description of key information

An acute oral LD50 of 300 - 400 mg/kg bw in rats was determined for hydroxylammonium sulphate. The studies all indicate that animals displayed cyanosis and methaemoglobinaemia. No data on the acute inhalation toxicity of hydroxylammonium nitrate or analogues were located. An acute dermal LD50 of 70 mg/kg bw was identified for hydroxylammonium nitrate in rabbits. An acute dermal LOAEL of 10 mg/kg bw of hydroxylammonium sulphate was determined in the rat and rabbit based on methaemoglobinaemia.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1950
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted prior to establishment of standardised guidelines, also unclear calculations of LD50
Qualifier:
no guideline followed
Principles of method if other than guideline:
White mice (10/sex/dose) were orally administered hydroxylammonium hydrochloride and observed for 72 hours. No further details reported.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
mouse
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
No data.
Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
Hydoxylammonium hydrochloride was given in 0.5 - 2 % aqueous solution so that the amount of liquid introduced for all the mice lay between 0.3 and 0.5 ml.
Doses:
200, 300, 400, 500 and 600 mg/kg.
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 72 hours.
- Frequency of observations and weighing: Not stated.
- Necropsy of survivors performed: Not stated.
Statistics:
Not stated
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
ca. 419 other: mg/kg
Based on:
dissolved
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 408 other: mg/kg
Based on:
dissolved
Mortality:
See table.
Clinical signs:
Not stated.
Body weight:
Not stated.
Gross pathology:
Methaemoglobin was observed in the dead animals.

Mortality of animals from the administration of different doses of hydroxylammonium hydrochloride.

Dose (mg/kg)

Mortality (male)

Mortality (female)

200

0/10

0/10

300

3/10

4/10

400

7/10

6/10

500

9/10

6/10

600

10/10

10/10

Calculated LD50 (mg/kg)

408

419

 

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The calculated LD50s are not reflective of the mortality observed in the study. The authors calculated an LD50 for male and female mice of 408 and 419 mg/kg. However from the mortality reported, the true LD50 should lie between the doses of 300 and 400 mg/kg for both male and female mice.
Executive summary:

In an acute oral toxicity study, groups of white mice (10/sex/dose) were given a single oral dose of hydroxlammonium hydrochloride at doses of 200, 300, 400, 500 and 600 mg/kg bw and observed for 72 hours. The authors calculated an LD50 for male and female mice of 408 and 419 mg/kg bw. However, the calculated LD50 is not reflective of the actual mortality reported in the study. The LD50 for both male and female mice was determined to be between 300 - 500 mg/kg bw. This reliability of this study is considered to be reliable with restrictions as the study was conducted prior to the establishment of standardised guidelines, however the calculated LD50s should be interpreted with caution.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
Studies were conducted prior to the establishment of guidelines or standardised methods, however they were reported in sufficient detail to identify an LD50.

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:
key study
Study period:
1980-1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No details on study method or GLP status are available in the study report.
Qualifier:
no guideline followed
Principles of method if other than guideline:
No data provided.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Type of coverage:
open
Sex:
not specified
Dose descriptor:
LD50
Effect level:
70 mg/kg bw
Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Hydroxylammonium nitrate is acutely toxic via the dermal route, with and LD50 of 70 mg/kg bw identified in rabbits.
Executive summary:

Hydroxylammonium nitrate is acutely toxic via the dermal route, with and LD50 of 70 mg/kg bw identified in rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
70 mg/kg bw
Quality of whole database:
Studies did not follow standardised guidelines, however they were well reported. Three studies did not use doses that were sufficient to determine an LD50.

Additional information

The acute oral toxicity of hydroxylammonium hydrochloride was determined to be between 300 - 400 mg/kg bw in rats. This chemical is considered to be a suitable analogue for hydroxylammonium nitrate, therefore read-across of data has been used. Of the two other acute oral studies located, one study identified a lower LD50 in cats, however the test species was a none-standardised species in acute toxicity testing, furthermore cats have been associated with greater formation of methaemoglobin indicating that they are potentially a more sensitive test species. This value indicates that classification with Acute Tox 4 (LD50 50 -300 mg/kg bw).

An acute dermal LD50 of 70 mg/kg bw was identified for hydroxylammonium nitrate in rabbits. An acute dermal LOAEL of 10 mg/kg bw of hydroxylammonium sulphate was determined in the rat and rabbit based on methaemoglobinaemia.

One study implied that the acute dermal toxicity of hydroxylammonium sulphate was dependent upon the nature of the exposure. The test chemical evidently had greater toxicity when applied under an occlusive patch compared to semi-occlusive, although the authors do not explain the observation. Of the four dermal toxicity studies, three reported adverse effects including skin irritation and haemorrhagic necrosis in rats and rabbits. A dermal LOAEL of 10 mg/kg bw was determined in both the rat and rabbit based on methaemoglobinaemia, rats also displayed splenomegaly at this dose, in another study at 1500 mg/kg, alteration in the gross pathology of rabbits were observed although no methaemoglobinaemia was observed. One study in rabbits (400 mg/kg bw 50% aqueous solution, occlusive, 24 hours) reported no adverse effects, however as the weight of evidence and existing classification of irritation and toxicity of hydroxylammonium sulphate exist this study was disregarded.

The toxicity observed after the oral and dermal administration of hydroxylammonium nitrate and its analogues were similar to effects observed after acute administration via intraperitoneal administration in rats.


Justification for selection of acute toxicity – oral endpoint
Of the studies located, this was considered the most reliable in terms of study design and data reporting. The other studies available were either in cats (which although more prone to methaemoglobinaemia and therefore potentially a more sensitive species) are a non-regulatory species for acute toxicity testing or had a higher LD50. The calculated LD50 for hydroxylammonium hydrochloride in this study was not consistent with the data reported, however using the raw data and LD50 of between 300- 400 mg/kg bw can be determined.

Justification for selection of acute toxicity – dermal endpoint
This study was performed on the test substance itself.

Justification for classification or non-classification

Hydroxylammonium nitrate has a harmonised classification of Acute Tox 4*, Harmful if swallowed and Acute Tox 3*, Toxic in contact with skin.