Dimethyl sulphate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with restirctions. Minor deviation from guideline: - According to the guideline the grading scale of Draize should be used in order to grade the ocular irritation, but a different grading scale was used in this study.

Data source

Reference

Reference Type:

publication

Title:

Evaluation of the ocular-irritation potential of 56 compounds

Author:

Guillot, J.O: et al.

Year:

1982

Bibliographic source:

Food Chem. Toxic. Vol., 573 - 582.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye 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-value: approx. 1.0
No further significant information was stated.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

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

Test system

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
A dose of 0.1 ml of dimethyl sulfate was instilled as a organic phase of a 50:50 (v.v) aqueous solution by means of a 1 ml steril polypropylene syringe (from Boston Dickinson (UK) LTd. Wembley, England).
No further information on the amount/concentration applied was stated.

Duration of treatment / exposure:

7 days

Observation period (in vivo):

Observation were recorded at 1 hr and 1, 2, 3, 4 and 7 days after instillation

Number of animals or in vitro replicates:

6 male rabbits

Details on study design:

The test substance was instilled into the lower conjunctival cul-de-sac of one eye of each rabbit; the other eye constituted the control.

REMOVAL OF TEST SUBSTANCE
- Washing: Rinsing was carried out with Dacryoserum (from Chibret Laboratories, Paris), a solution pf boric acid (1.8 g), sodium borate (0.002 g) in 100 ml rose distilled water QSP. An alternative, generally that recommended by the manufacturer, was used when the use of Dacryoserum was contra-indicated by the available information on the nature of the test material. Approxinately 20 ml of the rinsing solution at about 20 °C was applied to the test eye and to the control using a plastic wash-bottle.

Three trails were conducted with the test substance. Everytime another group of animals was used.
Trail 1: test substance was not removed after instillation
Trail 2: test substance was removed 30 seconds after instillation
Trail 3: test substance was removed 4 seconds after instillation

SCORING SYSTEM:
A scoring system based on AFNOR recommendation was used throughout with modifications where appropriate.
At each observation time lesions of the conjunctiva, iris and cornea were scored separately using a numerical system based on that of Kay & Calandra (1962), the sum of these scored being the individual ocular irritation index (IOI) for each animal. Calculation of the mean(and standard deviation) of the IOI values obtained at any one time gave the mean ocular irritation index (MOI). The greatest MOI obtained over the range of observation times was identified as the acute ocular irritation index (AOI), which was used for the preliminary classification of a substance in one of six categories between "non-irritating" and "extremely irritant" (see attachment AFNOR_scale). Where severity of lesions prevented an accurate reading, two values were calculated, a minimum taking all impossible readings as and a maximum assuming the highest possible scor e for all such readings. The maximum value was used for irritation classification.
Recalulation of the AOI value of the test substance taken on the basis of the reading taken (without rinsing) at the observation times specified in the OECD protocol (only 1, 24, 72 hr after instilllation) was conducted.

No further information on study design was stated.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: AOI

Basis:

mean

Time point:

other: 24 hr

Score:

109

Max. score:

109

Reversibility:

not reversible

Remarks on result:

other: No rinsing

Results 2

Irritation parameter:

other: AOI

Basis:

mean

Time point:

other: 24 hr

Score:

106.67

Max. score:

106.67

Reversibility:

not reversible

Remarks on result:

other: rinsing after 30 seconds

Results 3

Irritation parameter:

other: AOI

Basis:

mean

Time point:

other: 24 hr

Score:

100.17

Max. score:

100.17

Reversibility:

not reversible

Remarks on result:

other: rinsing after 4 seconds

Irritant / corrosive response data:

The animals treated with dimethyl sulfate were killed after day 7, because of the severity of the lesions.

Other effects:

No data

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dimethyl sulfate was classifed as corrosive.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is classified as risk of serious damage to eyes.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 1.