Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it was well conducted and documented and generally follows OECD Guideline 420.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1958

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
yes
Remarks:
maximum dose exceeded guideline recommended dose; animal fasting was not reported; animals were not weighed; pathology and clinical observations were generalized across dose levels of all chemicals tested
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ethanethiol (ethyl mercaptan)
- Analytical purity: gas chromatographic analysis showed the chemical to be essentially pure

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: local commercial breeder
- Weight at study initiation: 180 to 220 grams
- Diet (e.g. ad libitum): Rockland Rat Diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: one week

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE : No vehicle used

MAXIMUM DOSE VOLUME APPLIED: 3360 mg/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: doses were at geometric progression ( factor 1.26 to 2.0)
Doses:
210, 420, 840, 1680, and 3360 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observed on days 1, 2, 3, 5, 10, and 15 no weighing was conducted
- Necropsy of survivors performed: yes
- Other examinations performed: pathology
Statistics:
LD50 calculated by the method of Weil (Weil, C.S.: Tables for Convenient Calculation of Median-Effective Dose (LD50 or ED50) and Instruction in Their Use. Biometrics, 8: 249-304 (1954).)

Results and discussion

Preliminary study:
No data reported
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
682 mg/kg bw
95% CL:
517 - 900
Mortality:
Mortality occurred in all animals by 7 hours of administration for the 3360 mg/kg dose and day 5 for the 1680 mg/kg dose. Four of the five animals died in the 840 mg/kg dose level; and no mortality occurred at the 420 and 210 dose levels.
Clinical signs:
Toxicity signs included sedative action, and maximal sublethal doses resulted in deep comatose sleep for approximately 48 hours. Diarrhea was also pronounced for the highest doses.
Body weight:
No data reported
Gross pathology:
Gross pathology generally did not show significant gross or microscopic tissue changes. All animals that survived near lethal doses and were sacrificed within 20 days post-treatment, frequently showed pathologic changes which, although inconsistent, were indicative of liver and kidney damage. Microscopic examination revealed occasional marked changes in the kidneys of rats which included: degeneration with swelling and some necrosis of the tubular epithelium, thickening of Bowman’s capsule, and hyaline deposition in glomerular tufts. More often only minor lesions with varying degrees of cloudy swelling of the tubules and hyaline casts in the lumina were present. In general, liver changes were characterized by lymphocytic infiltration, occasional necrotic foci with small hemorrhages, and varying degrees of fatty degeneration. Only rarely did tissue studies show significant pathologic conditions as the result of relatively small doses of the chemical.
Other findings:
No data reported

Any other information on results incl. tables

 Toxicity Data for Rats Following Single Oral Dose of Ethanethiol

Dose (mg/kg)

Cumulative Mortality following Administration for the Day

1

2

3

5

10

15

210

0/5

0/5

0/5

0/5

0/5

0/5

420

0/5

0/5

0/5

0/5

0/5

0/5

840

2/5

2/5

2/5

2/5

3/5 (7th)

4/5 (11th)

1680

4/5

4/5

4/5

5/5

 

 

3360

5/5 (all dead 4 to 7 hrs)

 

 

 

 

 

LD50(mg/kg)

1034

 

 

 

 

682

Confidence Limits

667-1603

 

 

 

 

517-900

 

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study, groups of Wistar male rats (5/sex) were given a single oral dose of ethanethiol undiluted at doses of 210, 420, 840, 1680, or 3360 mg/kg bw and observed for 15 days (Fairchild & Stokinger, 1958). The oral LD50 was determined to be 682 mg/kg bw in males. This study is classified as Toxicity Category IV by EU classification.
Executive summary:

In an acute oral toxicity study, groups of Wistar male rats (5/sex) were given a single oral dose of ethanethiol undiluted at doses of 210, 420, 840, 1680, or 3360 mg/kg bw and observed for 15 days (Fairchild & Stokinger, 1958). 

 

Toxicity signs included sedative action, and maximal sublethal doses resulted in deep comatose sleep for approximately 48 hours. Diarrhea was also pronounced for the highest doses. Gross pathology generally did not show significant gross or microscopic tissue changes. Survivors of near lethal doses showed changes which, although inconsistent, were indicative of liver and kidney damage. Body weights were not measured. The oral LD50 was determined to be 682 mg/kg bw in males. This study is classified as Toxicity Category IV by EU classification.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it was well conducted and documented and generally follows OECD Guideline 420.