Hydroxylammonium chloride

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

On the toxicity of Hydroxylamine

Author:

Riemann, H.

Year:

1950

Bibliographic source:

Acta pharmacol. 6:285-292

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

12 females and 6 males received daily for 6 days/week a supplement of the test substance, which was added to milk as a solution over a period of 178 days.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxylammonium chloride

EC Number:

226-798-2

EC Name:

Hydroxylammonium chloride

Cas Number:

5470-11-1

Molecular formula:

ClH.H3NO

IUPAC Name:

hydroxyammonium chloride

Test material form:

solid

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: About 3 weeks old
- Weight at study initiation: Females: 45 - 59 g; Males: 35 - 59 g
- Housing: The animals were individually housed.
- Diet: Standard diet consisting of casein (20%), dry yeast (15%), starch (55%), salt mixture (5%) and lucerne meal (5%), ad libitum. In addition, the rats were frequently fed raw carrot, lettuce or apple.

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test substance was added to milk as a solution (pH 5.2) partly neutralized with sodium hydroxide.

PREPARATION OF THE DOSING SOLUTION
- Rate of preparation of the dosing solution: The solution for the drinking study was prepared daily.
- Mixing appropriate amounts with: The doses of the test substance were adjusted to be proportional to the weight of the rats. The rats with an average body weight of 30 - 70 g received 10 mg of the test substance (corresponding to 333 - 142 mg/kg bw/d and a mean value of 237.5 mg/kg bw/d), those with an average weight of 70 - 110 g received 20 mg of the test substance (corresponding to 285 - 181 mg/kg bw/d and a mean value of 233 mg/kg bw/d), those with an average weight of 110 - 150 g received 30 mg of the test substance (corresponding to 272 - 200 mg/kg bw/d and a mean values of 236 mg/kg bw/d) and the rats with an average weight > 150 g received 40 mg of the test substance (corresponding to 266 mg/kg bw/d).

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

178 days

Frequency of treatment:

Daily, 6 days/week

Doses / concentrations

Remarks:

range: 233 - 266 mg/kg bw/d

No. of animals per sex per dose:

12 females and 6 males

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

BODY WEIGHT: Yes, the body weight was recorded at the beginning and after 5 months.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, after 178 days the rats were killed with chloroform, frozen and kept at -20 °C for up to 30 days, after which they were dissected. The rats were kept wrapped up so that they could not lose water and were dissected after partial thawing. The organs were examined macroscopically, and the following organs were weighed: heart, lungs, liver, spleen, kidneys, adrenals and thyroid.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

The relative spleen weights were distinctly increased in treated females (1.645%) and males (1.56%) when compared with control females (0.469%) and males (0.316%), respectively. The relative thyroid weights were considerably reduced in females (0.038%) and males (0.032%) compared with control females (0.065%) and males (0.055%), respectively.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

A considerable development of the spleen and a marked reduction of the thyroid were observed in the animals of the treatment group. These findings correlate with the distinct increase of the relative spleen weights and with the strong induction of the relative thyroid weights.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Effect levels

Key result

Dose descriptor:

LOAEL

Effect level:

233 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

gross pathology

organ weights and organ / body weight ratios

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

233 mg/kg bw/day (nominal)

System:

haematopoietic

Organ:

spleen

thyroid gland

Treatment related:

yes

Applicant's summary and conclusion

Conclusions:

CLP: STOT RE 2, H373 (Annex VI harmonized classification)

The registrant follows the harmonised classification, thus the available data with the test substance meet the classification criteria according to Regulation (EC) 1272/2008.