Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 June - 11 July, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Ditetrahydrofurylpropane
- Lot/batch No.: 6-7B09
- Analytical purity: 99.7%
- Substance type: Clear colourless liquid
- Physical state: liquid
- Purity test date: 09 February 2007
- Expiration date of the lot/batch: 09 February 2010
- Storage condition of test material: At room temperature in the dark
- Stability under storage conditions: Stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: males 257-287 g; females 181-198 g
- Fasting period before study: not applicable
- Housing: Individually housed in labeled Macrolon cages (MIII type) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 - 22.7°C
- Humidity (%): 39 - 86%; Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- % coverage: approx. 10%
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was cleaned of residual test substance using tap water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (2 ml/kg) body weight.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/viability twice daily; body weights on day 1 (pre-administration, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.

Clinical signs:
Hunched posture, piloerection, chromodacryorrhoea, ptosis, and/or lethargy were noted in four males and 2 females on Days 1 and/or 2.

Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of Ditetrahydrofurylpropane in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

In an acute dermal toxicity study performed according to OECD 402 test guidelines, Ditetrahydrofurylpropane was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Hunched posture, piloerection, chromodacryorrhoea, ptosis, and/or lethargy were noted in four males and 2 females on Days 1 and/or 2. The body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of Ditetrahydrofurylpropane in Wistar rats was established to exceed 2000 mg/kg body weight.