3,4-dihydro-2-methoxy-2H-pyran

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Reference 3

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,4-dihydro-2-methoxy-2H-pyran

EC Number:

224-698-3

EC Name:

3,4-dihydro-2-methoxy-2H-pyran

Cas Number:

4454-05-1

Molecular formula:

C6H10O2

IUPAC Name:

2-methoxy-3,4-dihydro-2H-pyran

Details on test material:

- Name of test material (as cited in study report): Methoxydihydropyran
- Physical state: liquid
- Analytical purity: ca. 96%
- Impurities (identity and concentrations): 4% dimer acrolein, traces of acrolein and methylvinylether
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not reported
- Storage condition of test material: not reported

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Mean weight at study initiation: 147 g for males and 133 g for females
- Fasting period before study: ca. 16 h before application
- Housing: max. 5 rats/cage
- Diet (e.g. ad libitum): Standard pellet diet for rat and mouse
- Water: ad libitum
- Acclimation period: 3-7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 50-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle (mg/ml): 100, 215, 316, 383, 464, 681, undiluted
- Amount of vehicle (if gavage): 10 ml/kg bw



DOSAGE PREPARATION: The test substance was diluted with 0.5% solution of aqueous CMC to give the desired concentrations.

Doses:

1000, 2150, 3160, 3830, 4640, 6810, 10000 mg/kg bw

No. of animals per sex per dose:

5, except in the lowest doses where only 5 males (1000 mg/kg bw) or 5 females (2150 mg/kg bw) were used.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were observed before 15 min and after 15 min, 1h, 2h, 4h, 5h and 24 h of application and daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

Statistical analysis were made according to Finney DJ, 1971, Probit-Analysis, p 1-150 (Published by the Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London)

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 740 mg/kg bw

95% CL:

3 530 - 3 970

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

3 890 mg/kg bw

95% CL:

3 660 - 4 140

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

3 600 mg/kg bw

95% CL:

3 280 - 3 950

Mortality:

1000 mg/kg bw: 0/5 males;
2150 mg/kg bw: 0/5 females;
3160 mg/kg bw: 0/5 males and 1/5 females within 24 h;
3830 mg/kg bw: 2/5 males within 24 h and 3/5 females within 48 h;
4640 mg/kg bw: 5/5 males within 24 h and 5/5 females within 48 h;
6810 mg/kg bw: 5/5 males and 5/5 females within 24 h;
10000 mg/kg bw: 5/5 males and 5/5 females within 24 h

Clinical signs:

other: 1000 mg/kg bw: animals showed apathy, mild to strong ataxia and closure of eyelids; from 2150 mg/kg bw onwards: animals showed apathy, reduced or no reaction to external impulses, mild to strong ataxia, narcosis like state with reduced or no upright surfa

Gross pathology:

In the deceased animals, reddening and hardening of intestinal mucosa were observed. In one rat of the 6810 mg/kg bw dose group, hematoma in the intestinal mucosa was observed. In the 10000 mg/kg bw dose group, dark red lung in one rat and mottled liver in 2 rats were observed. No alterations were observed in the sacrificed animals.

Applicant's summary and conclusion

Executive summary:

This study was conducted according to guideline and is reliable without restrictions. Seven groups of male and female rats were administered with 1000, 2150, 3160, 3830, 4640, 6810, 10000 mg/kg bw of the test substance. The acute LD50 of the test substance was found to be 3740 mg/kg bw for male and female animals.

Clinical signs included apathy, reduced or no reaction to external impulses, mild to strong ataxia, narcosis like state with reduced or no upright surface reflexes, lapsed muscular tone, reduced or no reaction to pain, and decreased fecal content. These signs were reversible within 4 days after application. Normal body weight gain was observed in the surviving animals. Grossly, reddening and hardening of intestinal mucosa were observed in the deceased animals. No alterations were observed in the sacrificed animals.