Tetrahydrothiophene

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

0.3 ml of THT solution was applied to the skin of rats for 14 days

GLP compliance:

no

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:

- Supplier: Société Nationale des Pétroles d'Aquitaine
- Name of test material (as cited in study report): Tétrahydrothiophène
- Physical state: liquid
- Analytical purity: no data
- Lot/batch No.: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: St Denis de Pile (33), France
- Age at study initiation: no data
- Weight at study initiation: 160-180 g
- Housing: by free
- Diet (ad libitum): bouchons de régime UAR
- Water (ad libitum): tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-1
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Type of coverage:

open

Vehicle:

arachis oil

Details on exposure:

TEST SITE
- Area of exposure: flank
- surface: 4 cm²
- Type of wrap if used: none
- Time intervals for shavings or clipplings: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.3 ml
- Concentration (if solution): 3, 10, 30 or 100%
- Constant volume or concentration used: yes

VEHICLE
- Justification for use and choice of vehicle (if other than water): solubility

USE OF RESTRAINERS FOR PREVENTING INGESTION: no data

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
9, 30, 90 and 300 mg/animal
Basis:
other: Nominal per animal

Doses / concentrations 2

Remarks:

Doses / Concentrations:
ca. 2.25, 7.5, 22.5 and 75 mg/cm²
Basis:
nominal per unit area

Doses / concentrations 3

Remarks:

Doses / Concentrations:
ca. 40, 160, 450 and 1550 mg/kg bw/d
Basis:
nominal per unit body weight

No. of animals per sex per dose:

3

Control animals:

no

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: No

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily

BODY WEIGHT: Yes
- Time schedule for examinations: day 1, 5 and 14

FOOD CONSUMPTION: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: No
HISTOPATHOLOGY: No

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No effect.

BODY WEIGHT AND WEIGHT GAIN
No effect at 2.25, 7.5, 22.5 mg/cm², a decrease of the body weight day on day 5 at 75 mg/cm2.

SKIN IRRITATION
Slight desquamation at 75 mg/cm² (100%) but no irritation.

Effect levels

1

Dose descriptor:

NOAEL

Remarks:

systemic toxicity

Effect level:

450 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male

Basis for effect level:

other: decreased of the body weight gain at 75 mg/cm² NOAEL = 22.5 mg/cm²

2

Dose descriptor:

NOAEL

Remarks:

skin irritation

Effect level:

22.5 mg/cm² per day (nominal)

Based on:

act. ingr.

Sex:

male

Basis for effect level:

other: Some skin desquamation but no irritation at 75 mg/cm²

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

0.3 ml of 3, 10, 30 and 100% tetrahydrothiophene solutions in arachid oil (equivalent to 2.25, 7.5, 22.5 and 75 mg/cm² or 40, 160, 450 and 1550 mg/kg bw/d) was applied daily to the skin of groups of 3 rats for 14 days. A decrease of the body weight gain and a desquamation of the skin but no irritation were only observed with pure (100%) THT. No effect was observed at lower concentrations. The NOAEL for systemic toxicity and skin irritation was 22.5 mg/cm² (or 450 mg/kg bw/d).