Diethyl sulphide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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 according to GLP

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

occlusive dressing, test temperature

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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 sulphide
- 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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Age at study initiation: young adults
- Weight at study initiation: 201 to 213g for males and 238 to 285 for females (on day 0 of study)
- Fasting period before study: data not available
- Housing: individually in suspended stainless steel cages
- Diet: Purina Certified Rodent chow #5002, 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: 62 to 71°F (# 16.7 to 21.7°C)
- Humidity: 37 to 57%
- Air changes: 10 to 12 changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light


IN-LIFE DATES: From 22-DEC-1993 to 05-JAN-1994

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal trunk area
- % coverage: 10%
- Type of wrap if used: 4 ply porous gauze dressing backed with plastic wrap (occlusive binding)


REMOVAL OF TEST SUBSTANCE
- Washing: residual test material was removed using gauze moistened with distilled water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
- Concentration: undiluted

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw (limit test)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> clinical signs: 2 times on study day 0 (postdose) and daily thereafter (day 1-14)
> mortality: twice daily, in the morning and afternoon
> dermal observations: animals were observed for erythema and edema following patch removal on day 1 and daily thereafter
> body weight: prior to dosing on day 0 and on days 7 and 14
- Necropsy of survivors performed: yes

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no mortality

Mortality:

No mortality occurred during the limit test.

Clinical signs:

other: The most notable clinical abnormalities observed during the study included dark material around the facial area, urine stain and dermal irritation at the site of test article application.

Gross pathology:

No significant gross internal findings were observed at necropsy on study day 14.

Any other information on results incl. tables

Table 1: Number of animals dead and with evident toxicity and time range within which mortality occurred

 

Dose (mg/kg bw)	Mortality (# dead/total)			Time range of death (hours)	Number with evident toxicity (#/total)
	Male	Female	Combined		Male	Female	Combined
2000	0/5	0/5	0/10	-	5/5	5/5	10/10

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD0 of methyl ethyl sulphide was estimated to be greater than 2000 mg/kg in the rat. No mortality was observed.

Executive summary:

The single-dose dermal toxicity of methyl ethyl sulfide was evaluated in Sprague-Dawley rats (similar to OECD test guideline 402 and according to GLP). A limit test was performed in which one group of 5 male and 5 female rats received a single dermal administration of the test article at the dose of 2000 mg/kg bw. Following dosing, the limit test rats were observed daily and weighed weekly. A gross necropsy examination was performed on all limit test animals at the time of scheduled euthanasia (day 14). No mortality occurred during the limit test. The most notable clinical abnormalities observed during the study included dark material around the facial area, urine stain and dermal irritation at the site of the test application. Body weight gain was noted for the majority of animals during the test period. No significant gross internal findings were observed at necropsy on day 14.

The acute dermal LD₀ of methyl ethyl sulfide was estimated to be greater than 2000 mg/kg bw in the rat.

This study received a Klimisch score of 1 and is classified as reliable without restriction because the study design is similar to OECD testing guideline recommendations and it followed GLP.