Dimethyl sulphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Comparable to guideline study with acceptable restrictions: - In this study only a mean score, primary cutenous irritant index, was calculated, which was used for the classification of the test substance according to the AFNOR scale. This is not according to OECD. - According to the guideline, a single dose is applied to the skin of the animals. In this study two patches with the dose were applied to the skin of the animals. -According to the guideline, the test material should be removed at the end of the exposure time. In this study, it was not mentioned, if this was done. - According to the guideline tabulation of irritation response data for each individual animal for each observation time period should be stated. In this study only a mean score including all investigated animals was given.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Evaluation of the cutaneous-irritation potential of 56 compounds

Author:

Guillot, J.P. et al.

Year:

1982

Bibliographic source:

Fd. Chem. Toxic. Vol. 20: 563-572

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

See "Rationale for reliability"

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl sulphate

EC Number:

201-058-1

EC Name:

Dimethyl sulphate

Cas Number:

77-78-1

Molecular formula:

C2H6O4S

IUPAC Name:

dimethyl sulfate

Details on test material:

- Name of test material (as cited in study report): Dimethyl sulfate
- Physical state: Colourless liquid
- pH: approx. 1.0
No further information on test material was stated.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Roucher SA, Couhé
- Weight at study initiation: ca. 2.5 kg
No further information on test animals was stated.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: A dose of 0.5 ml of the organic phase of a 50/50 (v/v) aqueous solution of dimethyl sulfate was applied onto two approx. 6 cm^2 gauze pads.
No further information on amount/concentration was stated.

Duration of treatment / exposure:

4 hr

Observation period:

Macroscopic observation were made at 1, 24, 48, and 72 hr after patch removal.. Further readings at day 7 and day 14 were added in cases of pronounced irritation, to evaluate the possible reversibility of the lesions.

Number of animals:

6 male rabbits

Details on study design:

TEST SITE
- Area of exposure and type of wrap if used: Each rabbit was clipped over the back and flanks with a fine toothed electric clipper (Aesculap Type V 42 947), to give a precise cut (height 0.05 mm) without causing mechanical irritation of the skin. For the application of the test item, two sterile four-layered hydrophilic-gauze pads were placed on the skin of each rabbit, one pad on the right flank and one on the left side. The pads were held in place with adhesive tape.

REMOVAL OF TEST SUBSTANCE
Nothing was stated


SCORING SYSTEM: Each treated area was scored for erythema and oedema using a numerical system (0-4 in each case according to severity) based on that described by Draize, Woodard & Calvery (1948).

No further details on study design were stated.

Results and discussion

In vivo

Results

Irritation parameter:

other: Primary cutaneous irritation index

Basis:

mean

Time point:

other: 1, 24, 48, 72 hours

Score:

5.98

Max. score:

8

Reversibility:

not fully reversible within: 14 days

Irritant / corrosive response data:

The lesions showed only slight regression by day 14, when erythema was still clearly visible and oedema was occasionally recorded.

Other effects:

No data

Any other information on results incl. tables

The scores obtained for erythema and oedema at both of the treated sites in all six animals at the reading times were totalled. The sum obtained was then divided by the total number of readings to provide a mean score termed the primary cutaneous irritation index (PCI). The total number of readings (erythema + oedema) were 48 corresponding to two application sites on six animals at 1, 24, 48 and 72 hr after removal of the patches. The slightly different AFNOR scale (PCI below 0.5, non-irritant; 0.5 - 3. slightly irritant; 3 -5, moderately irritant; 5 - 8, severly irritant) was used to interpret the results.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dimethyl sulfate was considered to be corrosive.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is classified as skin corrosive.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 1A.