Hydroxylammonium nitrate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study not conducted to GLP or following a standardised guideline

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

2008

Materials and methods

Principles of method if other than guideline:

Female rats (10/female/dose) were exposed via a single dermal application for 24 hours to hydroxylammonium sulphate at either 10, 100 or 500 mg/kg. The chemical was moistened with water and held in contact with the skin by wrapping the torso of the rat with a polyethylene bandage. An additional group of animals (10/female) received the test material via an subcutaneous injection (1% aqueous solution) to act as a rough indication of complete dermal absorption.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxylammonium sulphate

IUPAC Name:

Hydroxylammonium sulphate

Details on test material:

Purity > 98%.

Test animals

Species:

rat

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

No data.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Remarks:

Test material was moistened with water

Details on dermal exposure:

Female rats were exposed for 24 hours to a single application of hydroxylammonium sulphate moistened with water. The test material was held in contact with the skin by wrapping the torso of the rat with a polythene bandage.

Duration of exposure:

24 hours.

Doses:

10, 100 and 500 mg/kg

No. of animals per sex per dose:

10

Control animals:

other: positive control

Details on study design:

Animals were observed twice each day for gross signs of toxicity. Blood samples were collected on day 2 and analysed for methaemoglobin. on days 4 and 14 blood samples were analysed for erythrocyte, leukocyte, platelet and reticulocyte counts. Total haemoglobin, hematocrit, mean corpuscular haemoglobin concentrations were also determined.

Statistics:

No data.

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

> 500 mg/kg bw

Mortality:

No mortality was observed.

Clinical signs:

Skin irritation of moderate incidence and to a lesser extent necrosis and sloughing were evident.

After 24 hours, rats (all doses) became paler, this persisted for up to 6 days after application. Cyanosis was not observed. Other signs of toxicity included a brown staining of the nares, mouth and forepaws and yellow staining of the anogenital area. Lacrimation was also observed.

Body weight:

Not reported.

Gross pathology:

Principle findings at necropsy included a high incidence of enlarged and darkened spleens regardless of the dose level of route of exposure.
Gross effects on the liver were minimal or absent.

Other findings:

Blood methaemoglobin levels were measured after 2 days and were found to be statistically higher than controls. Heinz bodies were not observed in circulating erythocytes.

Applicant's summary and conclusion

Conclusions:

Bis(hydroxylammonium)sulfate resulted in skin irritation, necrosis and sloughing. Exposed animals also displayed methaemoglobin and were a paler colour than control animals. At necropsy, animals had enlarged and darkened spleens. A LOAEL of 10 mg/kg bw can be derived based on mutiple effects. An LD50 could not be identified due to lack of mortality at the highest dose.

Executive summary:

Female rats were administered bis(hydroxylammonium) sulfate via a single occluded dermal application of either 10, 100 or 500 mg/kg bw for 24 hours. All doses resulted in skin irritation, necrosis and skin sloughing as well as methaemoglobin which was evident after 2 days. All animals also displayed splenomegaly, spleens were also much darker. This study is considered reliable (with restriction), therefore a LOAEL of 10 mg/kg bw can be derived based on mutiple effects. Bis(hydroxylammonium) sulfate is therefore considered a dermal irritant and an agent that causes methemoglobin in rats by this study design.