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Toxicological information

Acute Toxicity: dermal

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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

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.