Ethyl methyl sulphide

Endpoint summary

Description of key information

Skin irritation
The potential irritant and/or corrosive effects of methylethyl sulphide were evaluated on New Zealand White rabbits (study similar to OECD testing guideline and according to GLP) (Douds, 1994c). Each of six rabbits received a 0.5 ml dose of the test article as a single dermal application. The dose was held in contact with the skin under a semi-occlusive binder for an exposure period of four hours. Following the exposure period, the binder was removed and the remaining test article was wiped from the skin using gauze moistened with distilled water. Test sites were subsequently examined and scored for dermal irritation for up to 14 days following patch removal.
The mean scores at 24, 48 and 72 hours were:
- for erythema: mean score = 1.5
- for edema: mean score = 1.85
The effects were completely reversible after 7 to 14 days.
Additional dermal findings noted during the period included irritation observed in taped area outside the test site and desquamation, which were noted on 6/6 and 5/6 test sites, respectively.
Methylethyl sulphide is considered to be a slight irritant to the skin of the rabbit.

Eye irritation
The potential eye irritant and/or corrosive effects of methylethyl sulphide were evaluated on New Zealand White rabbits (method similar to OECD testing guideline and according to GLP) (Douds, 1994d). Each of six rabbits received a 0.1 ml dose of the test article in the conjunctival sac of the right eye. The contra lateral 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 as follow:
- Cornea: 0.9
- Iris: 0.3
- Conjonctivae (redness): 2.0
- Chemosis: 1.4
All the effects were completely reversible at the end of the observation period (up to day 14).

Respiratory tract irritation
No sign of respiratory tract irritation was observed in the acute inhalation toxicity study in rats (Colin and Jackson, 1988).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 15-NOV-1993 to 03-MAR-1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mohican Valley Rabbitry, Loudonville, Ohio
- Age at study initiation: adults
- Weight at study initiation: 1.924 to 2.130 kg for males and 2.286 to 2.582 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: 65 to 70°F (#18.3 to 21.1°C)
- Humidity: 33 to 49%
- Air changes: 10 to 12 air changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light


IN-LIFE DATES: From 18-NOV-1993 to 02-DEC-1993

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: unexposed area served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: undiluted

Duration of treatment / exposure:

4 hours

Observation period:

up to 14 days

Number of animals:

6 (3 males and 3 females)

Details on study design:

TEST SITE
- Area of exposure: approximately 1 inch x 1 inch (# 2.54 cm x 2.54 cm)
- % coverage: data not available
- Type of wrap if used: the test article was administrated under the gauze patch. The gauze patch was held in contact with the skin at the cut edges with a non-irritating tape. Removal and ingestion of the test article was prevented by placing an elastic wrap over the trunk and test area (semi-occlusive binding). The elastic wrap was then further secured with adhesive tape around the trunk at the cranial and caudal ends.


REMOVAL OF TEST SUBSTANCE
- Washing: residual test article was removed using gauze moistened with distilled water.
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: day 7 to day 14

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1.85

Max. score:

4

Reversibility:

fully reversible within: day 7 to day 10

Irritant / corrosive response data:

Exposure to the test article produced well-defined erythema and very slight to moderate edema on 6/6 test sites at the 1 hour scoring interval. The dermal irritation generally diminished during the remainder of the test period and resolved completely in all animals by study day 14. Additional dermal findings noted during the period included irritation observed in taped area outside the test site and desquamation, which were noted on 6/6 and 5/6 test sites, respectively.

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	Erythema	Edema
	Max. score: 4	Max. score: 4
60 min	2/2/2/2/2/2	2/2/2/1/3/2
24 h	2/2/2/2/3/2	2/2/2/2/3/2
48 h	1/2/1/1/2/1	2/2/2/2/2/2
72 h	1/1/1/1/1/1	1/1/2/1/1/2
Average 24h, 48h, 72h	1.3/1.7/1.3/1.3/2/1.3 Mean score: 1.5	1.7/1.7/2/1.7/2/2 Mean score: 1.85
Day 7	0/1/1/0/1/1	0/0/1/0/0/1
Day 10	-/0/0/-/0/1	-/0/0/-/0/0
Day 14	-/-/-/-/-/0	-/-/-/-/-/0
Reversibility*)	c	c
Average time (unit) for reversion	Day 7 to Day 14	Day 7 to Day 10

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

Interpretation of results:

Category 3 (mild irritant)

Conclusions:

Methyl Ethyl Sulfide is considered to be a slight irritant to the skin of the rabbit.

Executive summary:

The potential irritant and/or corrosive effects of Methyl Ethyl Sulfide were evaluated on New Zealand White rabbits (study similar to OECD testing guideline and according to GLP). Each of six rabbits received a 0.5 ml dose of the test article as a single dermal application. The dose was held in contact with the skin under a semi-occlusive binder for an exposure period of four hours. Following the exposure period, the binder was removed and the remaining test article was wiped from the skin using gauze moistened with distilled water. Test sites were subsequently examined and scored for dermal irritation for up to 14 days following patch removal.

The mean scores at 24, 48 and 72 hours were:

- for erythema: mean score = 1.5

- for edema: mean score = 1.85

The effects were completely reversible after 7 to 14 days.

Additional dermal findings noted during the period included irritation observed in taped area outside the test site and desquamation, which were noted on 6/6 and 5/6 test sites, respectively.

Methyl Ethyl Sulfide is considered to be a slight irritant to the skin of the rabbit.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

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

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

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 48h to day 7

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 24h to day 7

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: Day 7 to day 14

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

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.

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

Interpretation of results:

Category 2A (irritating to eyes)

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 as follow:

- Cornea: 0.9

- Iris: 0.3

- Conjonctivae (redness): 2.0

- Chemosis: 1.4

All the effects were completely reversible at the end of the observation period (up to day 14) .

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

According to the available skin, eye and respiratory tract irritation data, ethyl methyl sulphide should be classified as irritant to the eyes (category 2) following REGULATION (EC) No 1272/2008.