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Acute Toxicity: dermal

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acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study not conducted to GLP or following a standardised guideline

Data source

Reference Type:
secondary source

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

Constituent 1
Reference substance name:
Hydroxylammonium sulphate
Hydroxylammonium sulphate
Details on test material:
Purity > 98%.

Test animals

not specified
Details on test animals or test system and environmental conditions:
No data.

Administration / exposure

Type of coverage:
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.
10, 100 and 500 mg/kg
No. of animals per sex per dose:
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.
No data.

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 500 mg/kg bw
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

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.