Tetrahydrothiophene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 798.1100 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton-Dutchland, Inc., Denver, PA
- Age at study initiation: at least 8-week old
- Weight at study initiation: 2.6-2.9 kg for males and 2.5-3.1 kg for females- Fasting period before study:
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): Lab Rabbit Chow HF, Purina #5326
- Water (e.g. ad libitum): tap water
- Acclimation period: 21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-70
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Preparation of Animals:
On the day before dosing the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The skin remained intact, no abrasions were made.

Administration of Test Material:
The material was applied directly onto the exposed skin of the animal, and spread evenly over the entire area. Gauze was then wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve, designed to contain the test material without leakage or undue pressure. The sleeve was secured with tape and Elizabethan collars were placed on all animals to prevent ingestion of the test material or disruption of the wrappings.
Following approximately 24 hours of exposure, the wrappings were removed and the test site wiped free of excess test material.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

A single dose was administered to each animal, followed by 14 days of observations.

EXPERIMENTAL EVALUATION
Viability Check: Twice Daily

Observations of Pharmacologic and Toxicologic Signs:
Approximately 1, 2 and 4 hours after dosing and daily thereafter for fourteen days

Body Weights:
Pre-test, at the time of clipping (weights used for calculation of doses)
Days 7 and 14

POSTMORTEM
All animals surviving at termination of the observation period (Day 14) were killed by an intravenous overdose of sodium pentobarbital and examined grossly. All abnormalities were recorded but no tissues were saved.

Statistics:

None

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived throughout the study. Therefore, the dermal LD0 of Tetrahydrothiophene in rabbits is greater than 2000 milliqrams per kilogram of body weight.

Clinical signs:

Most animals exhibited severe dermal effects at the dose site (necrosis followed by eschar formation, fissuring and/or exfoliation of the eschar tissue) which persisted throughout the study.
Most animals exhibited hyperpnea on the day of dosinq. Other signs seen in one or two animals on the day of dosing included fine tremors, nasal discharge, dyspnea, arythmic respiration and red eyes. Several animals were noted to have decreased food consumption on Days 1, 2 and/or 3. This may represent an effect of test material administration or it may be related to some difficulties which were encountered with the water supply on Day 2 (low pressure) and Day 3 (temporary discontinuation of water to females). Most animals were free of significant signs of toxicity from Day 4 through study termination (Day 14), although two animals exhibited mucoidal stool and/or decreased food consumption between Days 10 and 13.

Body weight:

Most animals exhibited slight body weight losses at Day 7, but most gained weight between Days 7 and 14. One male exhibited a continuous weight loss over the study.

Gross pathology:

Gross postmortem observations confirmed the presence of dermal lesions discussed previously. Unusual observations included surface irregularities (wrinkling) of the spleen in five animals, discolored kidneys (mottled tan) in three animals and fissures in the liver in two animals. Other observations were similar to those seen in control animals in this laboratory or were considered to represent normal physiological variation.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD0 of Tetrahydrothiophene in rabbits is greater than 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study performed according to EPA guideline #OTS 798.1100 and GLP, Tetrahydrothiophene was administered to male and female New-Zealand rabbits at the dose level of 2000 mg/kg. All animals survived throughout the study. Most animals exhibited severe dermal effects at the dose site (necrosis followed by eschar formation, fissuring and/or exfoliation of the eschar tissue) which persisted throughout the study. Most animals exhibited hyperpnea on the day of dosinq. Other signs seen in one or two animals on the day of dosing included fine tremors, nasal discharge, dyspnea, arythmic respiration and red eyes. Gross postmortem observations confirmed the presence of dermal lesions discussed previously. Unusual observations included surface irregularities (wrinkling) of the spleen in five animals, discolored kidneys (mottled tan) in three animals and fissures in the liver in two animals. The dermal LD0 of Tetrahydrothiophene in rabbits is greater than 2000 mg/kg body weight.