Hydroxylammonium chloride

Endpoint summary

Description of key information

Available data is insufficient to conclude the repeated toxicity of hydroxylamine hydrochloride.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: performed to non-standard protocol, but contirbuting to assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

24 female and 12 male rats, about 3 weeks old, were divided equally into an experimental group and a control group. They were weighed and each animal was then transferred to a separate oage.
free access to the following diet :
The animals were fed as much whole milk as they would drink and
........................... casein 20 %
dry yeast ........................ 16 .
staroh ........................... 66 .
salt mixture ..................... 6 .
lucerne meal.. .................... 5 .
The salt mixture consisted of:
.................. sodium chloride. 16 Yo
magnesium sulphate.. ............. 30 .
prim. sodium phosphate ........... 32 .
tert. calcium phosphate ........... 9 .
calcium lactate ................... 12 .
ferricitrate ....................... 1 .
In addition, the rats were frequently fed raw carrot, lettuce or apple.

Route of administration:

other: oral: in milk

Vehicle:

not specified

Details on oral exposure:

The rats in the experimental group received daily for 6 days each week supplement of hydroxylamine hydrochloride, which was added to the milk as a solution (pH 6.2) partly neutralized with sodium hydroxide.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

178 days

Frequency of treatment:

once daily

Remarks:

Doses / Concentrations:
rats of an average weight of 30-70 g, 70-1 10 g, 110-160 g and above 160 g, received daily 10 mg, 20 mg, 30 mg and 40 mg of hydroxylamine hydrochloride, respectively.(equal to 333 to 380 mg/kg body weight)
Basis:
nominal in diet

No. of animals per sex per dose:

24 female and 12 male rats

Control animals:

yes, concurrent no treatment

Details on study design:

The doses have been calculated according to TARR and CARTER’S experimenta (1942) and are twice as large as the doses of sodium nitrite used by these authors in corresponding experiments. The hydroxylamine was given in these amounts, because the lethal dose of hydroxylamine hydrochloride is about twice that of sodium nitrite.
The feeding experiment with hydroxylamine lasted 178 days.

Observations and examinations performed and frequency:

The rats were at first weighed twice a week and later once a week, to the nearest gram.

Sacrifice and pathology:

After 178 days the rats were killed with chloroform, frozen and kept in a cold room 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. An attempt at histological examination of the organs had to be given up because of the structural changes during freezing.

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):

no effects observed

Food efficiency:

no effects observed

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

not specified

Ophthalmological findings:

not examined

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

enlargement of the spleen by 4 to 5 times and atrophy of the thyroid gland by about 50% were observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

There were no treatment-related effects on growth or general well-being in rats that were given 333 to 380 mg/kg body weight of the hydrochloride in their milk for 178 days. However, enlargement of the spleen by 4 to 5 times and atrophy of the thyroid gland by about 50% were observed.
The feeding of hydroxylamine did not prevent the rats from gaining weight in an apparently normal way.On the other hand, the feeding of hy-
droxylamine hydrochloride resulted in a considerable development of the spleen and a marked reduction in size of the thyroid of the hydroxylamine fed rats.

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Critical effects observed:

not specified

Conclusions:

Daily feeding of 0.33-0.38 g of hydroxylamine hydrochloride per kg of body weight for 178 days had no influence on the general condition and the growth-rate of the rats. On the other hand, a considerable development of the spleen and an essential reduction of the thyroid were observed.

Executive summary:

The 24 female and 12 male rats in the experimental group received daily for 6 days each week supplement of hydroxylamine hydrochloride at doses of 330 -380mg/kg/day, which was added to the milk as a solution (pH 6.2) partly neutralized with sodium hydroxide. The feeding experiment with hydroxylamine lasted 178 days. The feeding of hydroxylamine did not prevent the rats from gaining weight in an apparently normal way.On the other hand, the feeding of hy- droxylamine hydrochloride resulted in a considerable development of the spleen and a marked reduction in size of the thyroid of the hydroxylamine fed rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Only one publication was available, where daily feeding of 0.33-0.38 g of hydroxylamine hydrochloride per kg body weight for 178 days had no influence on the general condition and the growth-rate of the rats. On the other hand, a considerable development of the spleen and an essential reduction of the thyroid were observed.

However, existing study is not sufficient to draw a conclusion on the repeated toxicity of hydroxylamine hydrochloride as lacking of detailed information on clinical sign, clinical biochemistry, haematology, and micromacroscopic and microscopic pathological examination.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
only one study is available

Justification for classification or non-classification

Based on the results given in the study, it is inconclusive to make the classification for the repeated dose toxicity of hydroxylamine hydrochloride.