Diethyl sulphide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 15-NOV-1993 to 12-APR-1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study similar to OECD testing guideline and performed according to GLP

Justification for type of information:

Test result of a Methyl Ethyl Sulfide (CASN 624-89-5) has been used as this substance is considered to be similar on the basis of their chemical structure. Both substances contain one sulfur attached to a short carbon chain.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

6 animals used instead of 3 in the guideline

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl ethyl sulphide (CAS # 624-89-5)

IUPAC Name:

Methyl ethyl sulphide (CAS # 624-89-5)

Details on test material:

- Name of test material (as cited in study report): methyl ethyl sulfide
- Molecular formula (if other than submission substance): C3H8S
- Molecular weight (if other than submission substance): 76.16 g
- Smiles notation (if other than submission substance): C(SC)C
- InChl (if other than submission substance): InChI=1/C3H8S/c1-3-4-2/h3H2,1-2H3
- Substance type: pure active substance
- Physical state: clear colorless liquid
- Stability under test conditions: data not available
- Storage condition of test material: room temperature, protected from light

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Myrtle's rabbitry, Thompson station, TN
- Age at study initiation: adults
- Weight at study initiation: 3.052 to 3.117 kg for males and 2.590 to 3.228 kg for females
- Housing: individually in suspended stainless steel cages
- Diet: Purina certified rabbit chow #5322, ad libitum
- Water: municipal tap water treated by reverse osmosis or deionization, ad libitum
- Acclimation period: for a minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 53 to 72°F (# 11.7 to 22.2°C)
- Humidity: 40 to 57%
- Air changes: 10 to 12 air changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light


IN-LIFE DATES: From 03-JAN-1994 to 17-JAN-1994

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the contralateral eye remained untreated and served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: undiluted

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

up to 14 days

Number of animals or in vitro replicates:

6 (2 males and 4 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: any residual test material was gently rinsed from the eye using 0.9% physiological saline
- Time after start of exposure: 24 hours


SCORING SYSTEM: Draize scale


TOOL USED TO ASSESS SCORE: auxiliary light source + fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 48h to day 7

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 24h to day 7

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: Day 7 to day 14

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72h

Score:

1.4

Max. score:

4

Reversibility:

fully reversible within: Day 7 to day 14

Irritant / corrosive response data:

Exposure to the test article produced corneal opacity in 5/6 test eyes at the 24 hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention. The corneal opacity diminished during the remainder of the test period and resolved in all test eyes by study day 7. Iritis was observed in 6/6 test eyes by the 24 hour scoring interval and resolved completely in all animals by study day 7. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation generally diminished during the remainder of the test period and resolved completely in all animals by study day 14. Additional ocular findings included sloughing of the corneal epithelium, which was noted in 6/6 test eyes.

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0/0/0/0/0/0	1/1/1/1/1/0	2/2/1/2/2/2	2/2/2/2/2/2
24 h	0/2/2/2/2/2	1/0/0/0/1/1	2/2/2/2/2/2	1/2/2/2/2/2
48 h	0/0/0/0/2/2	1/0/0/0/0/1	2/2/2/2/2/3	1/1/1/1/1/2
72 h	0/0/0/0/0/2	0/0/0/0/0/1	1/2/2/2/2/2	1/1/1/1/1/2
Average 24h, 48h, 72h	0/ 0.7/0.7/0.7/1.3/2 Mean = 0.9	0.7/0/0/0/0.3/1 Mean = 0.3	1.7/2/2/2/2/2.3 Mean = 2	1/1.3/1.3/1.3/1.3/2 Mean = 1.4
7 days	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/2	0/0/0/1/0/1
10 days	-/-/-/0/-/0	-/-/-/0/-/0	-/-/-/0/-/2	-/-/-/0/-/1
14 days	-/-/-/-/-/0	-/-/-/-/-/0	-/-/-/-/-/0	-/-/-/-/-/0
Reversibility*)	c	c	c	c
Average time (unit) for reversion	48h to day 7	24h to day 7	Day 7 to day 14	Day 7 to day 14

 *) Reversibility: c. = completely reversible; = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes)

Remarks:

Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008

Conclusions:

Methyl ethyl sulfide is classified as irritating (category 2) to the eye according to criteria of REGULATION (EC) No 1272/2008.

Executive summary:

The potential eye irritant and/or corrosive effects of Methyl Ethyl Sulfide were evaluated on New Zealand White rabbits (method similar to OECD testing guideline and according to GLP). Each of six rabbits received a 0.1 ml dose of the test article in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 14 days following dosing.

The mean scores at 24, 48 and 72h were 0.9 for cornea, 0.3 for iris, 2.0 for conjonctivae (redness) and 1.4 for chemosis. All the effects were completely reversible at the end of the observation period (up to day 14). The mean score of conjonctivae is sufficient to classify the substance as irritating (category 2) according to REGULATION (EC) No 1272/2008.

This study received a Klimisch score of 1 and is classied as reliable without restriction because the study design is similar to OECD testing guidelines and was performed according to GLP.