Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 May - 11 June, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

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:
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: First group 2000 mg/kg: 153-159 g
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV 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): 19.3 – 21.3°C
- Humidity (%): 32 - 80%; 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

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (2 mL/kg) body weight and 300 mg/kg (0.3 mL/kg) body weight.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to the guideline
Doses:
2000 mg/kg and 300 mg/kg

No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and viability: twice daily. Body weights: Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- 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.
Statistics:
Not applicable, the method used is not intended to allow the calculation of a precise LD50 value

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg: first group 1/3, second group 2/3
At 300 mg/kg: first group 0/3, second group 0/3
The decedents and moribund animals were found between days 1 and 2.
Clinical signs:
2000 mg/kg: Lethargy, uncoordinated movements, flat and hunched posture, quick and slow breathing, shallow and labored respiration, piloerection, salivation, hypothermia, ptosis, scabs ear right.
300 mg/kg: Hunched posture, piloerection, quick breathing.
The surviving animals had recovered from the symptoms between Days 3 and 7.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. The incidence of slight body weight loss or reduced body weight gain in individual animals was considered not indicative of toxicity, based on the absence of any corroborative findings in these animals.
Gross pathology:
No test substance related abnormalities were found at macroscopic post mortem examination of the animals.
Incidental findings included cannibalism (missing ears) of one non-surviving animal.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 value of Ditetrahydrofurylpropane in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline the LD50 cut-off value was considered to be 2000 mg/kg body weight.
Executive summary:

In an acute oral toxicity study performed according to test guidelines OECD 423, Ditetrahydrofurylpropane was initially administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure additional groups of females were dosed at 2000, and 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15). Three (of the six) females dosed at 2000 mg/kg bw were found dead or sacrificed moribund between Days 1 and 2. No mortality occurred at 300 mg/kg bw. The surviving animals had recovered from the clinical symptoms between Days 3 and 7. The mean body weight gain shown by the surviving animals over the study period was considered to be normal. No substance related abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of Ditetrahydrofurylpropane in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline the LD50 cut-off value was considered to be 2000 mg/kg body weight.