Dimethoxymethane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The number of dose levels should be at least 3 according to OECD whereas only 1 had been tested in this limit study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Number of level doses (1) lower than a least 3 recommended by OECD

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethoxymethane

EC Number:

203-714-2

EC Name:

Dimethoxymethane

Cas Number:

109-87-5

Molecular formula:

C3H8O2

IUPAC Name:

dimethoxymethane

Details on test material:

- Name of test material (as cited in study report): C-01361
- Physical state: Colourless volatile liquid with chloroform odor
- Storage condition of test material: at room temperature
- Other: Receipt date: September 28, 1989

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: MohicanValley Rabbitry, Loudonville, Ohio, USA
- Age at study initiation: young adults
- Weight at study initiation: approximately 2.0 to 3.0 kg
- Fasting period before study: Not specified
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): Agway rabbit feed was provided to each animal ad libitum
- Water (e.g. ad libitum): fresh water was provided to each animal ad libitum
- Acclimation period: a minimum of 5 days prior to initiation of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-21°C
- Humidity (%): 40-60%
- Photoperiod (hrs dark / hrs light): 12-hour dark/12-hour light

IN-LIFE DATES: From: 10/24/89 To: 11/07/89

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: One test site measuring approximately 20 cm x 12 cm was selected on the dorsal area of the trunk (fur was clipped on the day prior to dosing) of animal
- % coverage: 10% of the animal's total body surface
- Type of wrap if used: plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw
- Concentration (if solution): Test material was applied undiluted

Duration of exposure:

24 hrs

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 (in dose group)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 15 days.
- Frequency of observations and weighing: On days 1, 8 and 15 for individual body weight; on the day of dosing and once daily therafter for the duration of the study for clinical signs; twice daily for mortality checks.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, body weight,mortality checks, gross necropsy examination.

Statistics:

The LD50 and 95% confidence lnterval were calculated separately for males, females and the combined sexes using a computer adaptation of Litchfield and Wilcoxon. Statistical analysis were not usedin this study.

Results and discussion

Preliminary study:

No mortality occured during the study.
No outward clinical signs of toxicity were observed during the test period. Transient incidences of slight erythema, soft stools, nasal discharge and fecal stains were noted during the test period.
All animals exhibited bodyweight gains during the study.
Gross necropsy revealed dark red and tanlobes of the lung (3/10 animals), white linear scars on the liver (2/10 animals), red fossy contents in the trachea (1/10 animals) and small gallbladder (1/10 animals). These findings appeared to be incidental. The pulmonary changes may have resulted from the method of sacrifice (t-61 euthanasiasolution).

Under the tested conditions, the rabbit acute dermal LD50 of Methylal was higher than 5000 mg/kg.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured during the study.

Clinical signs:

other: No outward clinical signs of toxicity were observed during the test period. Transient incidences of slight erythema, soft stools, nasal discharge and fecal stains were noted during the test period.

Gross pathology:

Gross necropsy revealed dark red and tanlobes of the lung (3/10 animals), white linear scars on the liver (2/10 animals), red fossy contents in the trachea (1/10 animals) and small gallbladder (1/10 animals). These findings appeared to be incidental. The pulmonary changes may have resulted from the method of sacrifice (t-61 euthanasiasolution).

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

Under the conditions of this fixed dosed study (limit test), the acute dermal LD50 of test article was determined to be greater than 5000 mg/kg bw in the rabbit.

Executive summary:

Four male and 4 female albino New Zealand rabbits were used in a limit test to assess dermal acute toxicity of merthylal.

Animals were kept during minimal 5-day acclimatization. Each animal was kept in an individual suspended stainless steel cage. Drinking fresh water and diet (Agway Prolab Rabbit Ration) were supplied ad libitum.

Approximatively 24 hours before the test, the fur of rabbits was clipped from the dorsal area of the trunk of each animal using small animal clippers. The clipped area dimension was approximatively 20 cm x 20 cm and constituted approximatively 10% of the total body surface of animals. The test item was applied, undiluted, for an exposure period of 24 hours, uniformaly over the clipped area, at a level of 5000 mg/kg bw, using a gauze dressing coverd with plastic wrap. A tubular stockinette sleeve was then positioned around the trunk of the animal and this was secured in place with tape.

After the removal of the patch, the treated area was rinsed with distilled water. The animals were observed for clinical signs on the day of dosing and once daily for the duration of the study. Mortality was recorded twice daily. Individual body weights were recorded on days 1, 8 and 15. All animals were gross necropsy examinated at the time of sacrifice (T61 euthanasia solution).

No mortality was recorded during the experiment. No outward clinical signs of toxicity were observed during the test period. Transient incidences of slight erythema, soft stools, nasal discharge and fecal stains were noted during the test period. All animals exhibited bodyweight gains during the study. Gross necropsy revealed dark red and tanlobes of the lung (3/10 animals), white linear scars on the liver (2/10 animals), red fossy contents in the trachea (1/10 animals) and small gallbladder (1/10 animals). These findings appeared to be incidental. The pulmonary changes may have resulted from the method of sacrifice.

Under experimental conditions of this fixed dosed study, the acute dermal LD50 of the test article methylal was determined to be higher than 5000 mg/kg bw in the rabbit.