Tetrahydrothiophene

Endpoint summary

Description of key information

Skin irritation was confined to erythema and edema during the first 24 hours following 4 hours of occluded contact. Eschar formation and superficial necrosis were noted in 4 of 6 rabbits during the first week. Recovery occurred  in most rabbits by Day 14. Eye irritation involving the conjunctiva and iris as well as corneal opacity were noted. These effects disappeared in 7-10 days. Inhalation exposure (acute and repeated) of rats elicited lacrymation, secretory increases and respiratory abnormalities but not histological changes in the respiratory tract.

Skin irritation

In a study performed according to EPA guideline #OPP 81-5 and GLP (Auletta, 1985), 0.5 ml of tetrahydrothiophene was applied for 4 hours under an occlusive dressing to the skin of 6 rabbits. Skin reactions were evaluated 30 min, 24, 48, 72 hours and 7, 10 and 14 days after the initial administration.
Tetrahydrothiophene produced only very slight (barely perceptible) to slight (well-defined) erythema and edema at 4.5 hours, but in four of the six animals tissue destruction (superficial necrosis and eschar formation) became evident subsequently (between 24 hours and 7 days). Two animals showed no tissue destruction and were free of significant irritation within 2 to 10 days after test material application. Of the four animals which developed necrosis and eschar formation, three exhibited exfoliation of the eschar tissue with no significant residual irritation by Day 10 or 14 and one continued to exhibit eschar tissue at study termination (Day 14).

According to these results, tetrahydrothiophene should be considered as irritant for the skin.

Eye irritation

In a study performed according to EPA guideline #OPP 81-4 and GLP (Auletta, 1985), 0.1 ml of tetrahydrothiophene was instillated in the conjunctival sac of 6 rabbits. Eye reactions were evaluated 1, 24, 48, 72 hours and 7 and 10 days after the initial administration. No wash was performed after application of the material.
Tetrahydrothiophene produced moderate to severe but reversible ocular irritation. All six animals exhibited severe conjunctival irritation (redness, chemosis, discharge, necrosis) and iritis and three exhibited corneal opacity and ulceration. Three animals were noted to have hair loss around the eye. The most severe conjunctival and iridial effects occurred one hour after instillation of the test material and corneal effects were most severe at 24 hours. Recovery was apparent, however, and all six animals were free of ocular irritation within 7 to 10 days after instillation of the test material. Mean scores over 24, 48 and 72h were 2.27, 1.16, 0.11 and 0.55 for conjunctival redness and chemosis, iritis and corneal opacity, respectively.

According to these results, tetrahydrothiophene should be considered as irritant for the eyes.

Respiratory tract

Lacrymation and nasal discharge were the most common clinical signs observed in acute (Terrill, 1986), sub-acute (Daly, 1986) and sub-chronique (Hardy, 1988) inhalation toxicity studies in rats. Histological signs of respiratory tract irritation were never observed.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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:

EPA OPP 81-5 (Acute Dermal Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton-Dutchland, Inc.3 , Denver, PA
- Age at study initiation: young adults
- Weight at study initiation: no data
- Housing: individually
- Diet (e.g. ad libitum): Lab Rabbit Chow HF (Purina #5326)
- Water (e.g. ad libitum): tap water
- Acclimation period: 20 days

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

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

Following approximately 4 hours of exposure, the wrappings and gauze square were removed and the test site gently wiped free of excess test material with gauze and water.

Observation period:

Approximately 4.5 hours (30 minutes after removal of wrappings), 24, 48 and 72 hours (3 days after the initial administration) and 7, 10 and 14 days after treatment or until no signs of Irritation were present.

Number of animals:

6

Details on study design:

At interval all sites were evaluated for erythema and edema or other evidence of derrnal irritation according to the Draize scoring system. Adjacent areas of untreated skin were used for comparison. Special notation was made of necrosis, eschar, or other evidence of irreversible alteration of tissue structure.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24+48+72 h

Score:

2.7

Max. score:

4

Reversibility:

other: Fully reversible within 14 days, excepted for 1 animals

Remarks on result:

other: Superficial necrosis and eschar formation in 4/6 rabbits

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24+48+72 h

Score:

1.05

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

Tetrahydrothiophene produced only very slight (barely perceptible) to slight (well-defined) erythema and edema at 4.5 hours, but in four of the six animals tissue destruction (necrosis and eschar formation) became evident subsequently (between 24 hours and 7 days). Two animals showed no tissue destruction and were free of significant irritation within 2 to 10 days after test material application. Of the four animals which developed necrosis and eschar formation, three exhibited exfoliation of the eschar tissue with no significant residual irritation by Day 10 or 14 and one continued to exhibit eschar tissue at study termination (Day 14).

Interpretation of results:

Category 2 (irritant)

Conclusions:

Tetrahydrothiophene should be considered as irritant for the skin.

Executive summary:

In a study performed according to EPA guideline #OPP 81-5 and GLP, 0.5 ml of Tetrahydrothiophene was applied for 4 hours under an occlusive dressing to the skin of 6 rabbits. Skin reactions were evalutated 30 min, 24, 48, 72 hours and 7, 10 and 14 days after the initial administration.
Tetrahydrothiophene produced only very slight (barely perceptible) to slight (well-defined) erythema and edema at 4.5 hours, but in four of the six animals tissue destruction (necrosis and eschar formation) became evident subsequently (between 24 hours and 7 days). Two animals showed no tissue destruction and were free of significant irritation within 2 to 10 days after test material application. Of the four animals which developed necrosis and eschar formation, three exhibited exfoliation of the eschar tissue with no significant residual irritation by Day 10 or 14 and one continued to exhibit eschar tissue at study termination (Day 14).
According to these results, tetrahydrothiophene should be considered as irritant for the skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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:

EPA OPP 81-4 (Acute Eye Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton-Dutchland, Inc.3 , Denver, PA
- Age at study initiation: young adults
- Weight at study initiation: no data
- Housing: individually
- Diet (e.g. ad libitum): Lab Rabbit Chow HF (Purina #5326)
- Water (e.g. ad libitum): tap water
- Acclimation period: 20 days

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

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Amount applied: 0.1 ml

Duration of treatment / exposure:

The appropriate amount of the test material was introduced into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for one second prior to releasing to prevent loss of material. The contralateral eye served as the control.

No wash was performed after application of the material. However, approximately 24 hours after application, the treated eye was rinsed to remove any residual test material.

Observation period (in vivo):

- Intervals:
Approximately 1, 24, 48 and 72 hours and 7 and 10 days after treatment, or until no signs of irritation were present.
- Method:
At interval the treated and control eyes were examined and scored for ocular reactions according to the Draize scale. Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for two observations. Unusual effects such as pannus, blistering of the conjunctiva, ulceration and other effects indicative of corrosive action were also noted when present.

Number of animals or in vitro replicates:

6

Details on study design:

Preparation of Animals:
On the day before dosing, both eyes of each animal were examined using fluorescein dye to check for presence of corneal ulceration. Just prior to test substance application, the eyes were examined again, but without fluorescein. Animals showing pre-existing corneal or conjunctival injury or irritation were not placed on study.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 + 48 + 72 h

Score:

2.27

Max. score:

3

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 + 48 + 72 h

Score:

1.16

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 + 48 + 72 h

Score:

0.11

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 + 48 + 72 h

Score:

0.55

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Tetrahydrothiophene produced moderate to severe but reversible ocular irritation. All six animals exhibited severe conjunctival irritation (redness, chemosis, discharge, necrosis) and iritis and three exhibited corneal opacity and ulceration. Three animals were noted to have hair loss around the eye. The most severe conjunctival and iridial effects occurred one hour after instillation of the test material and corneal effects were most severe at 24 hours. Recovery was apparent, however, and all six animals were free of ocular irritation within 7 to 10 days after instillation of the test material.

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

A transient conjunctivitis and/or corneal opacity are observed after acute instillation in the eye of rabbits.

Executive summary:

In a study performed according to EPA guideline #OPP 81-4 and GLP, 0.1 ml of Tetrahydrothiophene was instillated in the conjunctival sac of 6 rabbits. Eye reactions were evalutated 1, 24, 48, 72 hours and 7 and 10 days after the initial administration. No wash was performed after application of the material.
Tetrahydrothiophene produced moderate to severe but reversible ocular irritation. All six animals exhibited severe conjunctival irritation (redness, chemosis, discharge, necrosis) and iritis and three exhibited corneal opacity and ulceration. Three animals were noted to have hair loss around the eye. The most severe conjunctival and iridial effects occurred one hour after instillation of the test material and corneal effects were most severe at 24 hours. Recovery was apparent, however, and all six animals were free of ocular irritation within 7 to 10 days after instillation of the test material. Mean scores over 24, 48 and 72h were 2.27, 1.16, 0.11 and 0.55 for conjunctival redness and chemosis, iritis and corneal opacity, respectively.
According to these results, tetrahydrothiophene should be considered as irritant for the eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

In accordance with Regulation (EC) No 1272/2008, tetrahydrothiophene was classified Skin irrit. Cat 2 H315 and Eye irrit. Cat 2 H319.