2,4-dimethyl-4-phenyltetrahydrofuran

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

No guideline available in the report as the test has been performed prior to the OECD guideline. However it conforms to the OECD 401 guideline.

Principles of method if other than guideline:

No guideline available in the report as the test has been performed prior to the OECD guideline. However it conforms to the OECD 401 guideline.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

rel-(2R,4R)-2,4-dimethyl-4-phenyltetrahydrofuran

Cas Number:

99343-90-5

Molecular formula:

C12H16O

IUPAC Name:

rel-(2R,4R)-2,4-dimethyl-4-phenyltetrahydrofuran

Constituent 2

Reference substance name:

rel-(2S,4R)-2,4-dimethyl-4-phenyltetrahydrofuran

Cas Number:

99343-91-6

Molecular formula:

C12H16O

IUPAC Name:

rel-(2S,4R)-2,4-dimethyl-4-phenyltetrahydrofuran

Test material form:

liquid

Specific details on test material used for the study:

Name: Rhubafuran
Received on September 9, 1980
Stored in refrigerator until use
Appearance: Light-yellow liquid with a pungent odour

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Cpb:WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS (Cpb:WU; Wistar random)
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands.
- Age at study initiation: young adult
- Weight at study initiation: 92 to 168g for males and 94 to 170g for females.
- Fasting period before study: overnight before dosing
- Housing: in stainless-steel cages with grid-bottom and front
- Diet (e.g. ad libitum): Stock diet.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 °C +/- 1°C, well-ventilated

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Remarks:

Concentration in vehicle: 50 % (v/v)

Doses:

2381, 2877, 3422, 4117 and 4960 mg test material/kg bw diluted in a solution of propylene glycol (50% v/v).

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

After treatment, the rats received stock diet and tap water ad libitum. They were observed for signs of intoxication during a 14-day period after which autopsies were carried out on the survivors.
The LD50 was calculated according to the method of Weil (Biometrics 8 (1952), 249-263).
Each dose was expressed in milliliter per kg in the study.
Considering the relative density of the substance (0.992 g/cm3), the dose level was converted in miligramme per kg.

Results and discussion

Preliminary study:

The dose selection was performed based on a previous study (TNO, 1981b, Tentative determination of the acute oral toxicity of Rhubafurane in rats).
The undiluted test material was administered by gavage to ten males and ten females in one single dose of 4960 mg test material/kg bw.
Out of 10 males and 10 females, 7 males and 7 females succumbed within a 6 hours to 5 days period after treatment. The LD50 is determined to be lower than 4960 mg test material/kg bw.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 980 mg/kg bw

Based on:

test mat.

Mortality:

Death occurred between 6 hours and 5 days after treatment.
See the table of results below.

Clinical signs:

other: Within a few hours after dosing the rats showed sedation and signs of ataxia. Later on encrustations around eyes and nostrils, signs of emaciation and coma were frequently observed. Survivors recovered gradually and looked quite healthy again at the end o

Gross pathology:

Macroscopic examination of the survivors at autopsy did not reveal any treatment-related gross alterations.

Any other information on results incl. tables

Table 7.2.1/01. Dose applied and mortality results

Dose	Mortality
Test material	Number		%
(mg/kg)	males	females
2381	0/5	0/5	0
2877	1/5	1/5	20
3422	1/5	2/5	30
4117	2/5	4/5	60
4960	4/5	3/5	70

The LD50 of the test substance to male/female Wistar rats was found to be 3980 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the test conditions of this study, the oral LD50 of the test substance to male/female Wistar rats was estimated to be equal to 3980 mg/kg bw.
Therefore, the test material is classified Category 5 (H303: May be harmful if swallowed) according to the GHS, as the LD50 value is comprised between 2000 and 5000 mg/kg bw, and is not classified according to the Regulation (EC) No. 1272/2008 (CLP).

Executive summary:

In an acute oral toxicity study equivalent to the OECD test guideline No. 401, five males and five females Wistar (Cpb:WU) rats per dose were given the following dose level as a solution in propylene glycol (50% v/v): 2381, 2877, 3422, 4117 and 4960 mg test material/kg bw.

Mortality and clinical signs were monitored during the study, and all surviving animals were subjected to gross necropsy after a 14-day observation period.

 

Death occurred between 6 hours and 5 days after treatment. Within a few hours after dosing the rats showed sedation and signs of ataxia. Later on encrustations around eyes and nostrils, signs of emaciation and coma were frequently observed. Survivors recovered gradually and looked quite healthy again at the end of the observation period. Macroscopic examination of the survivors at autopsy did not reveal any treatment-related gross alterations.

 

Oral LD50 Males/Females = 3980 mg/kg bw (4.02 mL/kg bw)

The LD50 of the test substance to male/female Wistar rats was found to be 4.02 ml/kg bw, with a 95% confidence limits between 3.34 to 4.85.
Considering the relative density of the substance, the oral LD50 of the test substance to male/female Wistar rats was estimated to be equal to 3980 mg/kg bw.

 

Therefore, the test material is classified Category 5 (H303: May be harmful if swallowed) according to the GHS, as the LD50 value is comprised between 2000 and 5000 mg/kg bw, and is not classified according to the Regulation (EC) No. 1272/2008 (CLP).