Sodium sulphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Remarks:

old in vivo study

Type of information:

other: experimental data from literature data in read across

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Literature data

Data source

Reference

Reference Type:

publication

Title:

Interspecies variations in response to topical application of selected zinc compounds.

Author:

Lansdown A. B. G

Year:

1991

Bibliographic source:

Fd Chem. Toxic. Vol. 29, No. 1, pp. 57-64, 1991

Materials and methods

Principles of method if other than guideline:

The dermal irritancy of the substance was examined in three animal models. Macroscopic skin reactions, skin histological changes and epidermal keratin binding of the test material were observed after 5 d application to skin using open patch test.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Similar Substance 01

IUPAC Name:

Similar Substance 01

Test animals

Species:

mouse

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Animals: TO (outbred) and AG2 (inbred)
- Breeding: aminals were bred under barrier-maintained specified pathogen-free conditions at the Chafing Cross and Westminster Medical School. Male mice
- Age at study initiation: 8-10 wk old
- Diet: complete rodent diet (CRM, Biosure, Cambridge, UK)
- Water: deionized water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22±2°C
- Humidity: 55%
- Photoperiod: 12-h light/dark cycle

Test system

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes

Amount / concentration applied:

The concentrations used were those that had been shown to be non-irritant in preliminary acute studies in white (TO) mice (mice back skin was treated with 0.5 ml of the test compound at 0.1, 1.0, 10 or 20% and examined for erythema after 24 hr).

TEST SOLUTION
Test concentration: 1% (w/v)
Test solution was prepared 24 hr before use and stored at 4°C. The pH of each preparation was measured immediately before application.

Duration of treatment / exposure:

5 days

Observation period:

5 days post exposure

Number of animals:

8 groups of 6 animals, for open patch

Details on study design:

1) OPEN PATCH TEST:
TEST SITE
- Area of exposure: test sites (5 cm^2) were prepared in the mid-dorsal regions.
- Preparation test area: the hair coat was clipped closely and the skin cleansed with 70% alcohol and allowed to dry before treatment.
Animals were gently anaesthetized with ether until the test sites had dried.

SACRIFICE
24 h after the fifth daily treatment, animals were sacrificed and representative samples of each test and control skin sites were preserved in 10 % phosphate buffered formalin for histology. Thin sections cut along the anterior-posterior axis were stained with haematoxylin and eosin, or with morin dye, which fluoresces blue-green in the presence of zinc ions and ultraviolet light (to demonstrate zinc binding to epidermal keratin histologically).

2) EPIDERMAL CELL KINETICS:
The influence on the mitotic behaviour of the dorsal skin epidermis was examined.
The experiment was set up identically to the mouse experiment, except that groups of 5 A2G mice were used for each treatment regimen.
Twenty-four hr after the final treatment, each mouse received a single ip injection of 0.1 mg vincristine (Oncovin, Lilly, Basingstoke, Hants., UK) in 0.25 ml of normal saline (Bullough and Laurence, 1966).
The animals were killed by cervical dislocation after 4 hr and three strips of skin from the treatment sites were preserved in 10% formalin for histological examination. Sections were stained with haematoxylin and eosin, and arrested mitoses per 1000 cells were counted.
The mitotic index was calculated.

3) MICROBIOLOGY:
In view of the observation that certain compounds exhibit antibiotic properties, fresh skin samples were obtained from animals at the end of the experimental period. They were routinely smeared across sterile blood agar plates, incubated at 37°C, and examined for bacterial growths 24 hr later using standard criteria. Previous quality assurance studies have shown an absence of ectoparasites, mycoplasma and viral infections in animals bred and maintained in the animal facility of the Charing Cross and Westminster Medical School.

Results and discussion

In vivo

Results

Irritation parameter:

other: irritation

Basis:

animal: 6 animals

Time point:

other: 5 days

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Any other information on results incl. tables

Slight irritation (lower level of erythema) was observed in two out of six test animals after 5 d exposure. No reactions were observed in control group.

- Macroscopic observations in mouse skin exposed for 5 days: slight irritancy. Hair regrowth was possibly more advanced in sulphate.

- Histological changes in the skin following application in open patch tests: no evidence of damage.

- Morin fluorescence in skin: slight irritancy.

- Influence on epidermal cell proliferation in mouse skin: not significantly different from control group.

- Microbiology in the skin following treatment: Staphylococcus epidermidis and α-haemolytic streptococci. Animals treated with test substance induced negligible evidence of irritancy of epithelial hyperplasia.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Not irritating

Executive summary:

The dermal irritancy of Similar Substance 01 was examined in three animal models. Macroscopic skin reactions, skin histological changes and epidermal keratin binding of the test material were not observed after 5 d application to skin using open patch test.

Conslusion

No statistically significant epidermal hyperplasia in normal skin following topical application was observed.

Substance can be considered to be non-irritant.