Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
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: Studies 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
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
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 administrationENVIRONMENTAL CONDITIONS- Temperature (°C): 22-26- Humidity (%): 20-80- Air changes (per hr): not specified- Photoperiod (hrs dark / hrs light): 12/12IN-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 gauzeREMOVAL OF TEST SUBSTANCE- Washing (if done): rinsing with warm water- Time after start of exposure: 24 hours after exposureTEST MATERIAL- Amount(s) applied: 2.28 mL/kg- Concentration: undiluted
Duration of exposure:
24 hours
Doses:
2000 mg/kg bwt, 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 daysBody weights:Individual body weights were determined shortly before administration (day 0), weekly thereafter and on last day of study.Clinical signs:Recordings of clinical signs 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None observed
Clinical signs:
No significant local or systemic effects were observed.
Body weight:
No significant changes.
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 informationCriteria used for interpretation of results: other: EU DSD classification criteria (EU Directive 67/548/EEC)
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.