Registration Dossier

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:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
See "Rationale for reliability"
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

Resultsopen allclose all
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
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
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.