Tetrahydro-3-methylfuran

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

10 July 2009 to 19 August 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Studines were conducted according to generally valid and/or internationally accepted testing guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), Part B: Methods for the determination of toxicity and other health effects: Acute Toxicity (Dermal); Official Journal of the European Union, No. L 142

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrahydrofuran

EC Number:

203-726-8

EC Name:

Tetrahydrofuran

Cas Number:

109-99-9

IUPAC Name:

tetrahydrofuran

Details on test material:

- Name of test material (as cited in study report): tetrahydrofuran
- Test substance number: 99/0151-4
- Physical state: liquid/colorless, clear
- Analytical purity: >/= 99.8%
- Lot/batch No.: K38826031
- Stability under test conditions: the stability under storage conditions over the study period was guaranteed by the Sponsor
- Storage condition of test material: room temperature under nitrogen; light excluded
- Other: the density (g/mL) was reported as 0.879

Test animals

Species:

rat

Strain:

other: Wistar/Cr1:WI (Han) SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, Germany
- Age at study initiation: males, approx. 8 weeks; females, approx. 12 weeks
- Weight at study initiation: males, 225.8 +/- 6.46; females, 210.4 +/- 3.51
- Fasting period before study: none
- Housing: Makrolon cage, type III; singly housed
- Diet (ad libitum): VRF1(P); SDA Special Diets Services
- Water (ad libitum): tap water
- Acclimation period: at least 5 days prior to test chemical administration


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26
- Humidity (%): 20-80
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 13 July 2009 To: 28 July 2009

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm^2
- % coverage: at least 10% of the body surface area
- Type of wrap if used: four layers absorbent gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with warm water
- Time after start of exposure: 24 hours after exposure


TEST MATERIAL
- Amount(s) applied: 2.28 mL/kg
- Concentration: undiluted

Duration of exposure:

24 hours

Doses:

2000 mg/kg, single dose

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Route of application:
Single application to the clipped epidermis (dorsal and dorsolateral parts of trunk); covered with a semiocclusive dressing (four layers of absorbent gauze, Ph. Eur. Lohmann GmbH and Co. KG and Fixomull stretch, adhesive fleece, Beiersdorf AG) for 24 hours.

Observation period:
14 days

Body weights:
Individual body weights were determined shortly before administration (day 0), weekly thereafter and on last day of study.

Signs and symptoms:
Recordings of signs and symptoms were obtained several times on the day of administration, and at least once daily after each workday for individual animals.

Scoring of skin findings:
Individual readings 30-60 minutes after removal of semi-occlusive dressings (day 1); weekly thereafter and on the last day of observation.

Mortality:
A check for dead and moribund animals was made at least once each workday.

Assessment of skin reactions:
The evaluation of skin reactions was performed according to Draize, J.H. (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas (see Table 1).

Pathology:
Necropsy with gross pathology examination on the last day of the observation perod after sacrifice with carbon dioxide.

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Results and discussion

Preliminary study:

Clinical observations:
There was no mortality. No systemic or local effects of toxicity were noted. The mean body weights of all animals increased normally during the study.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None observed

Clinical signs:

other: No significant local or systemic effects were observed.

Gross pathology:

There were no macroscopic abnormalities noted in animals (5 males and 5 females) examined on the last day of observations.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the median lethal dose (LD50) of tetrahydrofuran after dermal application was found to be greater than 2000 mg/kg body weight in both male and female rats.

Under the dangerous substances directive (67/548/EC), this material would not be classified as toxic.

Executive summary:

In a dermal toxicity study in young adult Wistar rats (5 males and 5 females), exposure to 2000 mg/kg bw of undiluted tetrahydrofuran produced no mortality nor any clinical signs of toxicity. Mean body weights of animals increased normally throughout the study. The LD50 values was determined to be > 2000 mg/kg bw.