Tetrahydrothiophene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetrahydrothiophene

EC Number:

203-728-9

EC Name:

Tetrahydrothiophene

Cas Number:

110-01-0

Molecular formula:

C4H8S

IUPAC Name:

tetrahydrothiophene

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 Breeding laboratoryies Inc. (Wilmington, MA, USA)
- Age at study initiation: 9-12-week old
- Weight at study initiation: 268-360 g (males); 220-256 g (females)
- Fasting period before study: 18 h
- Housing: individually in suspended, stainless steel cages
- Diet (e.g. ad libitum): Purina Loaboratory Chow, 5001
- Water (e.g. ad libitum): municipal water
- Acclimation period: 15 or 21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67-76
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

800, 1000, 1250, 1600, 2000, 3125 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

EXPERIMENTAL EVALUATION
The following observations were made on animals which were dosed for LD50 determination.
Viability Check: Twice Daily
Clinical signs of toxicity: Approximately 1, 2, and 4 hours after dosing and daily thereafter for fourteen days.
Body Weights: Pre-fast (weights used for calculation of doses), Day 7 and Day 14.
Terminal: Any animals which did not survive for 14 days were weighed at the time of death or at the time they were found dead.

POSTMORTEM
Gross postmortem examinations were performed on all animals which died or were found dead during the study. All animals surviving at termination of the observation period (Day 14) were killed by carbon dioxide inhalation and examined grossly. All abnormalities were recorded but no tissues were saved.

Statistics:

LD50 was calculated using the following method: Miller, Lloyd C. and M.L. Tainter., Estimation of the ED50 and Its Error by Means of Logarithmic-Probit Graph Paper, Proc. Soc. Exp. Bio. Med. 57: 261-264 (1944).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 850 mg/kg bw

95% CL:

1 547 - 2 153

Mortality:

Dose levels, mortality and the estimated LD50 with 95% confidence limits were as follows:
Mortality
Dose Level male female total Time of Death
mg/kg
800 0/5 1/5 1/10 24 Hr
1000 0/5 0/5 0/10 -
1250 1/5 0/5 1/10 24 Hr
1600 0/5 3/5 3/10 24 Hr-Day 2
2000 2/5 4/5 6/10 24 Hr-28 Hr
3125 6/6 4/4 10/10 24 Hr-28 Hr

LD50 (mg/kg): 2000 1750 1850
95% Confidence
Limits (mg/kg): 1387- 1268- 1547-
2613 2232 2153

Clinical signs:

Signs seen in all groups during the 24 hours after dosing included ataxia, tremors, hypoactivity and/or prostration, oral discharge, various respiratory abnormalities and decreased food consumption. Two animals, one in the 1000 mg/kg group and one in the 2000 mg/kg group, had discolored (red or dark brown) urine. Other observations occurred sporadically. Although some abnormalities were still apparent on Days 2 and 3, most survivors were free of unusual signs from Day 4 through study termination (Day 14).

Body weight:

Most surviving males exhibited weight gains at Day 7, although several females in the 1000, 1250 and 1600 mg/kg groups showed slight weight losses. All surviving gained weight between Days 7 and 14; gains were generally comparable among groups.

Gross pathology:

Postmortem examinations of animals which were found dead revealed a variety of changes, primarily in the lungs and gastroinestinal tract. A few animals had red or black material in the stomach and intestine and red or black discoloration of the gastrointestinal mucosa. Several had apparent test material in the gastrointestinal tract. One animal in the 1250 mg/kg group had red fluid in the urinary bladder. Other changes in animals found dead appeared to represent autolytic changes. Changes in animals killed after 14 days were similar to those seen in control animals killed by carbon dioxide inhalation in the laboratory.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50's were 2000 (1387-2613) mg/kg, 1750 (1268-2232) mg/kg and 1850 (1547-2153) mg/kg for male, female and combined sex rats, respectively.

Executive summary:

In an acute oral toxicity study performed according to EPA guideline #OTS 798.1175 and GLP, tetrahydrothiophene was administered to male and female Sprague-Dawley rats at dose levels of 800, 1000, 1250, 1600, 2000, 3125 mg/kg.

Most surviving males exhibited weight gains at Day 7, although several females in the 1000, 1250 and 1600 mg/kg groups showed slight weight losses. All surviving gained weight between Days 7 and 14; gains were generally comparable among groups. Clinical signs of toxicity seen in all groups during the 24 hours after dosing included ataxia, tremors, hypoactivity and/or prostration, oral discharge, various respiratory abnormalities. Postmortem examinations of animals which were found dead revealed a variety of changes, primarily in the lungs and gastroinestinal tract.

The LD50's were 2000 (1387-2613) mg/kg, 1750 (1268-2232) mg/kg and 1850 (1547-2153) mg/kg for male, female and combined sex rats, respectively.