Tetrahydrothiophene

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation 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

Details on test material:

Source: Pennwalt Corporation
Batch number: 113-539-84
Purity: > 99%

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 Laboratories, Inc., Wilmington, MA
- Age at study initiation:
Males: 7-8 weeks
Females: 9-10 weeks
- Weight at study initiation:
Males: 209-291 g
Females: 202-220 g
- Fasting period before study:
- Housing: individually housed in stainless steel wire cages
- Diet (e.g. ad libitum): Purina Rodent Laboratory Chow #5001
- Water (e.g. ad libitum): tap water
- Acclimation period: 1 to 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67-76
- Humidity (%): 30-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The Plexiglas exposure chamber had a total volume of 100 liters. The chamber was operated dynamically at a calibrated air flow rate of 25 liters per minute (lpm). This flow rate was calculated to provide one complete air change every 4 minutes and a 99% equilibrium time of 18.4 minutes. Approximately 300 milliliters (mls) of the test substance was placed in each of two 500 ml bubblers fitted with impingers. House-supply air was delivered via a Dwyer flowmeter and a Nupro metering valve to the two bubblers and into a 3-neck flask. Additional diluted air was delivered to the 3-neck flask via a Nupro metering valve and a Dwyer flowmeter. The resultant vapor-laden air stream was directed from the 3-neck flask into the 100 liter Plexiglas exposure chamber.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Samples for determination of tetrahydrothiophene vapor exposure levels were taken using a MIRAN lA Ambient Air Analyzer and strip chart recorder (Fisher Recordall Series 5000). The exposure level of tetrahydrothiophene was determined by the resultant

Duration of exposure:

4 h

Concentrations:

0, 3090, 4400, 5260, 5670 and 6300 ppm (11142, 15866, 18968, 20446 and 22718 mg/m3, analytical concentrations)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

Five groups consisting of five male and five female Sprague-Dawley rats per group were exposed to an atmosphere containing the test subtance for four hours. All survivors were held for a 14-day post-exposure observation period.
A gross necropsy examination was performed on all animals dying spontaneously during the study and on all survivors at the end of the 14-day post-exposure observation period.
A control group also consisting of five male and five female Sprague-Dawley rats was included. These animals received a four-hour exposure to house-supply air only.

In-Life Observations:
Day 1 (Day of Exposure): All animals were observed individually prior to exposure, as a group at approximately fifteen minute intervals during the first hour of exposure, each one-half hour for hours 1 through 2 and hourly for the remainder of the exposure. All survivors were observed individually upon removal from the chamber (half-hour after exposure was completed) and 4 hours post-exposure. Detailed physical observations were recorded at each interval.
Days 2 through 15 (Post-exposure): Detailed observations were recorded for survivors once dailyl; viability was assessed twice daily.

Body Weight:
Day 1 (immediately prior to exposure) and on Days 2, 3, 4, 8, 11 and 15.

Postmortem:
A necropsy was performed on all animals dying spontaneously or sacrificed at the end of the post-exposure observation period. The gross postmortem examinations included the nasal passages, trachea, external surface, all orifices, the cranial cavity, carcass, the brain and spinal cord, the thoracic, abdominal and pelvic cavities and their viscera and the cervical tissues and organs.

Statistics:

A calculation of median lethal concentration and 95% confidence limits was performed according to the method of Litchfield and Wilcoxon.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

6 270 other: ppm (analytical)

95% CL:

5 180 - 7 590

Exp. duration:

4 h

Remarks on result:

other: = 22572 mg/m3

Effect levels 2

Sex:

male/female

Dose descriptor:

other: LOAEC for local irritation

Effect level:

3 090 ppm

Exp. duration:

4 h

Remarks on result:

other: = 11142 mg/m3. Lacrymation, nasal discharge and respiratory distress

Mortality:

Chamber Monitoring and Mortality:
The mean analytical and nominal exposure concentrations of tetrahydrothiophene along with the overall mortality in each test group are summarized as follows:

Mean Mean
Analytical Nominal
Group Concentration Concentration Mortality
(ppm) (ppm) #dead/#exposed
Male female
I 6300 9480 5/5 5/5
II-Control 0 0 0/5 0/5
III 3090 5460 0/5 0/5
IV 4400 6060 0/5 0/5
V 5260 8330 2/5 0/5
VI 5670 8170 1/5 1/5

The analytical concentrations were approximately two thirds of the nominal exposure concentrations. No reason for these differences was found. No aerosol was found during any exposure. The distribution of material in chamber was acceptable.

Based on the mean analytical concentration values of tetrahydrothiophene and resultant mortality, the LC50 values and 95% confidence limits were calculated to be:

Sex LC50 95% Confidence Limits
ppm
Combined Sexes
(males and females) 6270 5180 to 7590
Males 5900 4960 to 7010
Females 6700 5540 to 8100

Clinical signs:

other: 1. Exposure Period: Most animals exposed to 6300 ppm tetrahydrothiophene died during exposure. Lacrimination, respiratory distress, reduced activity, matted coat, prostration and poor condition were exhibited by these animals. Similar signs, except deat

Body weight:

Male body weights decreased or exhibited stasis through Day 3. Subsequently, increments for male body weight gain were normal (except at 5670 ppm between Days 8 and 11). In females, body weights decreased between Days 1 and 2. Subsequent female body weight gain increments were normal (except at 5260 and 5670 ppm in the periods 11-15 days and 8-11 days respectively). During the second week post-exposure, at 4400 and 5260 ppm, female body weight gains were decreased compared to control animals. These effects were considered treatment related. Second week post-exposure body weights for other groups were considered unremarkable.

Gross pathology:

A number of the tissues and organs for the animals which died during the study were discolored, primarily red, of various intensities. This finding was not considered to be unusual in animals which died and were not exsanguinated prior to postmortem examination.
The toxicological significance, if any, with respect to the test article, of the dark red lungs observed in the animals which died during the study, remains equivocal. The lungs of the animals which survived to the end of the study exhibited various discolorations which were observed in a number of the animals of all groups. These, and other findings which occured sporadically in the animals of this study, were not considered to be related to the test article.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A series of groups consisting of five male and five female Sprague-Dawley rats was exposed to tetrahydrothiophene vapors for four hours at mean analytical levels in the range of 3090 to 6300 ppm. The resultant median lethal concentration values were 6270 ppn for the combined sexes, 5900 ppm for males and 6700 ppm for females. This suggested that the test material was of comparable toxicity to both sexes.
Signs attributable to treatment included death, increased incidences of secretory responses, respiratory distress, reduced activity, matted coat, prostration, poor condition, ano-genital area staining and loss of body weight. Overall, the time-to-onset and time-to-recovery of these signs appeared to be related to exposure concentration.
Gross postmortem evaluations revealed darken, reddish lungs for decedents. The toxicological significance of this finding, if any, remains equivocal.

Executive summary:

A series of groups consisting of five male and five female Sprague-Dawley rats was whole-body exposed to tetrahydrothiophene vapors for four hours at mean analytical levels in the range of 3090 to 6300 ppm (11142 to 22718 mg/m³). The study was performed according to EPA guideline #OPP 81-3 and GLP (Terrill, 1986). Signs attributable to treatment included death, increased incidences of secretory responses, respiratory distress, reduced activity, matted coat, prostration, poor condition, ano-genital area staining and loss of body weight. Overall, the time-to-onset and time-to-recovery of these signs appeared to be related to exposure concentration. The resultant median lethal concentration values were 6270 ppm (22572 mg/m³) for the combined sexes.