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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not reported
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
Reviewers' note: The Japanese relevant authority have stated clearly in secondary summaries that this study was conducted in compliance with GLP. However, some pages, which may contain the confirmation of GLP compliance, are missing from the published study report."
Reviewer's note: The study report is a translation from Japanese and does not include the date of the study. However, the OECD SIDS references the study year as 2004.
GLP compliance:
yes
Remarks:
(Certificate is not included in the study report.
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrahydrofurfuryl alcohol
EC Number:
202-625-6
EC Name:
Tetrahydrofurfuryl alcohol
Cas Number:
97-99-4
Molecular formula:
C5H10O2
IUPAC Name:
tetrahydrofuran-2-ylmethanol
Details on test material:
- Name of test material (as cited in study report): Tetrahydrofurfuryl alcohol

- Physical state: colourless, transparent liquid

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan Inc. (795 Shimofurusawa, Atsugi-shi, Kanagawa)
- Age at study initiation: 10 weeks old
- Weight at study initiation: Step 1: mean bodyweight; 214 g (205-225 g)
Step 2: mean bodyweight; 215 g (207-219 g)
- Fasting period before study: No feeding performed from PM 5 on previous day of treatment to 3-hours after treatment.
- Housing: Test animals were bred in a stenless metal mesh cage (260W x 380D x 180H mm) in a barrier system animal room (No.8).
- Diet (e.g. ad libitum): Solid feed, labo MR stock, Nosan Corporation, Lot. No. 020765, ad libitum
- Water (e.g. ad libitum): Tap water sterilized by filteration with 1 µm diameter carteidge filter and UV radiation. ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(purified water)
Details on oral exposure:
VEHICLE;
The test substance is soluble in water, therefore, pharmacopoeia purified water was selected as vehicle.
Pharmacopoeia purified water: Kyoei Pharmaceutical Co., Ltd. Lot. No. 181376
- Concentration in vehicle: 20w/v%
- Amount of vehicle (if gavage): 10 mL per 1 kg of body weight
DOSAGE PREPARATION;
The test solution was prepared immediately before treatment.
Starting dose;
Fixed dose level was adopted according to OECD guideline 423 and dose level was set as 2000 mg/kg in accordance with the report that LD50 value by oral treatment of the test substance in rat was reported as 1.6 to 3.2 g/kg.
Doses:
2000 mg/kg bw Step 1
2000 mg/kg bw Step 2
No. of animals per sex per dose:
Step 1; 3 animals
Step 2; 3 animals
Control animals:
no
Details on study design:
Observation period was for 14 days following administration. Observation of clinical signs and confirmation of death were performed at least once an hour after the administration between 1 and 3 hours, and between 3 and 6 hours after administration on Day 1 (the day of administration). Observation was performed once each in the morning and in the afternoon on Day 2, once in the morning from Day 3 and later. Body weight was measured on Day 1 (immediately before administration), 4, 8 and 15. After observation on Day 15, animals were anesthetized by ether and euthanized and gross necropsy was performed on internal organs. Clinical sings only was observed daily on animals that were not administered.
Statistics:
No statistical analysis was carried out.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities occurred in response to treatment.
Clinical signs:
Mild hyptoni and a severe decrease in locomotor activity was observed on all animals within 1 hour after treatment. These findings disappeared on day-2 and no clinical signs were observed thereafter.
(see: Table 2)
Body weight:
Normal body weight gain took place during the observation period.
Gross pathology:
No gross change was observed at necropsy at end of the observation period.
Other findings:
There were no other findings.

Any other information on results incl. tables

Table 1: Mortality of female rates treated with tetrahydorfurfuryl alcohol

       In the single dose oral toxicity test

Step

Dose

(mg/kg)

Number of

animals treated

Number of animals that died

Mortality

Category

(GHS)

1 – 15 (days)

1

2000

3

0

0* / 3**

5

2

2000

3

0

0 / 3

*: Number of animals that died

**: Number of animals treated

GHS: Globally Harmonized Classification System

Table 2: Clinical signs of female rats treated with tetrahydrofurfuryl alcohol

in the single dose oral toxicity test

Step

Dose

(mg/kg)

Findings

Grade

Day

1

2

3

4 - 15

1

3

6(hrs)

1

2000

Number of animals examined

3

3

3

3

3

3

(A)

1

3

0

0

0

0

0

3

0

3

3

0

0

0

(B)

1

0

3

3

0

0

0

2

2000

Number of animals examined

3

3

3

3

3

3

(A)

1

3

0

0

0

0

0

3

0

3

3

0

0

0

(B)

1

0

3

3

0

0

0

A: Decreased locomotor activity

B: Hypeotonia

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An LD50 value of >2000 mg/kg bw is reported in a reliable study conducted according to current OECD guideline, but not in compliance with GLP.

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