Ethyl methyl sulphide

Endpoint summary

Description of key information

Oral route

In an acute oral toxicity study (similar to OECD testing guideline 401 and according to GLP) (Douds, 1994a), groups of fasted, young adults Sprague-Dawley rats (5/sex) were given a single oral dose of undiluted methyl ethyl sulphide by gavage at dose of 5000 mg/kg bw (limit test) and observed for 14 days. One male rat died on day 1. All other animals survived up to the end of the study. Clinical signs were observed in all animals: salivation, piloerection, wobbly gait, decreased activity, lacrimation, eyelids partially closed, transient incidences of urine stain, transient incidences of rales, rough haircoat, decreased/no defecation, dark material around the facial area, low food consumption. Gross internal findings noted at necropsy for the animal that died included clear yellow-red fluid contents in the urinary bladder, light green staining of glandular mucosa in the stomach and greenish-red mucoid contents in the entire tract of the small intestine. No gross internal findings were observed at necropsy on study day 14 for the surviving animals. The Oral LD50(combined males/females) was > 5000 mg/kg bw.

Dermal route

The single-dose dermal toxicity of methyl ethyl sulphide was evaluated in Sprague-Dawley rats (similar to OECD test guideline 402 and according to GLP) (Douds, 1994b). 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 sulphide was estimated to be greater than 2000 mg/kg bw in the rat.

Inhalation route

In an acute inhalation toxicity study performed according to the OECD guideline # 403 and GLP, no mortality and clinical sign of toxicity was observed in male and female rats exposed to an atmosphere concentration of 21.72 mg/l (6988 ppm) of methyl ethyl sulphide for 4 hours. At necropsy, dark areas were observed on lungs of 1 female rat (Colin and Jackson, 1988).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 15-NOV-1993 to 11-APR-1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to a recognised guideline and GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

limit test at 5000 mg/kg bw

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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: from 248 to 288 g for males and from 253 to 264 g for females (on day -1)
- Fasting period before study: yes (overnight)
- Housing: individually in stainless steel cages
- Diet: Purina certified Rodent chow #5002 ad libitum
- Water (e.g. ad libitum): municipal tap water treated by reverse osmosis or deionization, ad libitum
- Acclimation period: for a minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 62 to 72 °F (# 16.7 to 22.2°C)
- Humidity: 40 to 58%
- Air changes: 10 to 12 air changes per hour
- Photoperiod: 12 hrs dark / 12 rs light


IN-LIFE DATES: From 15-DEC-1993 to 29-DEC-1993

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 6 mL/kg

Doses:

5000 mg/kg bw

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, and daily thereafter
> body weight: prior to fasting (day -1), prior to dosing on day 0, for all surviving animals on day 7 and 14, or at the time for death
- Necropsy of survivors performed: yes

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

One male rat died on day 1. All other animals survived up to the end of the study

Clinical signs:

other: The most notable clinical abnormalities observed during the study included salivation which was noted in 8/10 animals on study day 0 only, piloerection noted in 8/10 animals during the study day 0 to 2 interval, wobbly gait noted in all test animals on st

Gross pathology:

Gross internal findings noted at necropsy for the animal that died included clear yellow-red fluid contents in the urinary bladder, light green staining of glandular mucosa in the stomach and greenish-red mucoid contents in the entire tract of the small intestine. No gross internal findings were observed at necropsy on study day 14 for the surviving animals.

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 deaths (day)	Number with evident toxicity (#/total)
	Male	Female	Combined		Male	Female	Combined
5000	1/5	0/5	1/10	Day 1	5/5	5/5	10/10

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU and GHS

Conclusions:

The acute oral LD50 of Methyl Ethyl Sulfide was estimated to be greater than 5000 mg/kg in the rat.

Executive summary:

In an acute oral toxicity study (similar to OECD testing guideline 401 and according to GLP), groups of fasted, young adults Sprague-Dawley rats (5/sex) were given a single oral dose of undiluted methyl ethyl sulfide by gavage at dose of 5000 mg/kg bw (limit test) and observed for 14 days. One male rat died on day 1. All other animals survived up to the end of the study. Clinical signs were observed in all animals: salivation, piloerection, wobbly gait, decreased activity, lacrimation, eyelids partially closed, transient incidences of urine stain, transient incidences of rales, rough haircoat, decreased/no defecation, dark material around the facial area, low food consumption. Gross internal findings noted at necropsy for the animal that died included clear yellow-red fluid contents in the urinary bladder, light green staining of glandular mucosa in the stomach and greenish-red mucoid contents in the entire tract of the small intestine. No gross internal findings were observed at necropsy on study day 14 for the surviving animals. The Oral LD₅₀(combined males/females) was > 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

GLP guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Albino rats, Spraque-Dawley. One control group and 1 test group each of 5 male and 5 female rats.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

By inhalation of a test atmosphere containing vapour of the test substance.
4 hours continuous whole-body exposure.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gas cromatography

Duration of exposure:

4 h

Concentrations:

21.72 mg/l

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

14 days post exposure

Statistics:

Not appropriate

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 21.72 mg/L air

Exp. duration:

4 h

Mortality:

There were no deaths during the study

Clinical signs:

other: (a) During exposure: No abnormalities. (b) During the observation period: No abnormalities

Body weight:

Slight loss of bodyweight or reduction of rate of bodyweight gain for one day following exposure.

Gross pathology:

Macroscopic pathology: Dark areas on lungs of 1 female rat exposed to METHYL ETHYL SULFIDE.

Other findings:

Food and water consumption: Food consumption was slightly reduced for 1 day following exposure. Possible slight elevation of water consumption for a few days following exposure in female rats only.
Lung weight to body weight ratio: The lung weight to body weight ratio for female rats exposed to METHYL ETHYL SULFIDE was higher than the control values. Males were unaffected.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU and GHS

Conclusions:

The 4h-LC0 in higher than 21.72 mg/l in both male and female rats

Executive summary:

In an acute inhalation toxicity study performed according to the OECD guideline # 403 and GLP, no mortality and clinical sign of toxicity was observed in male and female rats exposed to an atmosphere concentration of 21.72 mg/l (6988 ppm) of methyl ethyl sulfide for 4 hours. At necropsy, dark areas was observed on lungs of 1 female rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

21 720 mg/m³ air

Quality of whole database:

GLP guideline study

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 according to GLP

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

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

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

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.

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 deaths (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

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU and GHS

Conclusions:

The acute dermal LD0 of Methyl Ethyl Sulfide 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP guideline study

Justification for classification or non-classification

According to REGULATION (EC) No 1272/2008 and the available acute toxicity data, ethylmethyl sulphide don't warrant a classification for acute toxicity.