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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Reference 2

Reference Type:

publication

Title:

The Acute Toxicity of Methoxydihydropyran.

Author:

Dodd DE et al.

Year:

1988

Bibliographic source:

Vet Hum Toxicol 30: 545-550

Reference 3

Reference Type:

secondary source

Title:

3,4-Dihydro-2-methoxy-2H-pyran (CAS No. 4454-05-1)

Author:

OECD

Year:

2003

Bibliographic source:

cited in OECD SIDS 3,4-Dihydro-2-methoxy-2H-pyran for SIAM 16, 27-30 May 2003, Paris, France.

Reference 4

Reference Type:

publication

Title:

No information

Year:

2001

Bibliographic source:

cited in RTECS 01

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Occlusive dressing

GLP compliance:

not specified

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
- Analytical purity: 99.105%
- Impurities (identity and concentrations): 0.643% of the Methoxydihydropyran dimer and 0.037% acrolein
- Lot/batch No.: not reported
- Stability under test conditions: not reported
- Storage condition of test material: not reported

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: males 2564-2574 g and females 2522-2566 g
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Type of wrap if used: Polyethylene sheeting and VETRAP Bandaging tape


REMOVAL OF TEST SUBSTANCE
- Washing: no, residual test substance was removed with cleansing tissue.
- Time after start of exposure: 24 hrs

Duration of exposure:

24 h

Doses:

2, 4, 8 ml/kg bw (corresponding to 2000, 4000, 8000 mg/kg bw) Calculation based on density of the test substance (1 g/ml).

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice daily for signs of intoxication, body weight was measured before, at 7 and 14 days post exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 values were calculated by the moving average method described by Thompson (Bact Rev 11:115, 1947) and Weil (Drug Chem Toxicol 6:595, 1983).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 920 mg/kg bw

95% CL:

3 580 - 6 750

Mortality:

0/1, 1/5 and 5/5 animals (both male and females) died in the 2000, 4000, 8000 mg/kg bw dose groups, respectively. Most deaths occurred within a day of application or the day following removal of the dressing, except one female in the 4000 mg/kg bw dose group who died 8 days after removal of the dressing.

Clinical signs:

other: Signs observed in all doses were comatose appearance at 15 to 25 min, sluggishness during the 24 hr contact period, and labored breathing and emaciated appearance at 7 and 14 d.

Gross pathology:

Necropsy of animals that died revealed dark red lungs and red patches in the trachea. Survivors showed mottled pink or red discoloration of the lungs.

Other findings:

Local findings: Erythema and oedema were seen in some animals after removal of the occlusive dressing, with erythema persisting in a few animals for 7 d. A few animals that died from 8000 mg/kg bw had ecchymoses. Desquamation was seen at 7 and 14 day after exposure.

Applicant's summary and conclusion

Executive summary:

This study is comparable to the guideline and is reliable without restrictions. Undiluted test substance was applied to clipped skin of 10 rabbits (5 males and 5 females) under occlusive conditions for 24 h at concentrations of 2000, 4000 and 8000 mg/kg bw. 0/1, 1/5 and 5/5 animals (both male and females) died in the 2000, 4000 and 8000 mg/kg bw dose groups, respectively. The LD50 was found to be 4920 mg/kg bw for male and female animals. Signs observed in all doses were comatose appearance at 15 to 25 min, sluggishness during 24 hr contact period, and labored breathing and emaciated appearance at 7 and 14 d. Decrease in body weight gain was observed in the survivors. Necropsy of animals that died revealed dark red lungs and red patches in the trachea. Survivors showed mottled pink or red discoloration of the lungs.