Tetraethyl 2,2'-(1,4-phenylenedimethylidyne)bismalonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline conform GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetraethyl 2,2'-(1,4-phenylenedimethylidyne)bismalonate

EC Number:

228-726-5

EC Name:

Tetraethyl 2,2'-(1,4-phenylenedimethylidyne)bismalonate

Cas Number:

6337-43-5

Molecular formula:

C22H26O8

IUPAC Name:

1,3-diethyl 2-({4-[3-ethoxy-2-(ethoxycarbonyl)-3-oxoprop-1-en-1-yl]phenyl}methylidene)propanedioate

Test material form:

other: solid

Test animals

Species:

rat

Strain:

other: HanRcc: WIST(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ktd. CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: males - 9 weeks; females - 11 weeks
- Housing: individually in Makrolon type-3 cages with standard sofwood bedding
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3422 rat/mouse maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland), ad libitum
- Water (e.g. ad libitum): community tap water from Füllinsdorf, ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25. June To: 16. July 2008

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface.
Only those animals without injury or irritation on the skin were used in the test.
On test day 1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Application volume/kg body weight: 4 mL
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed.
All animals were re-shaved on test days 8 and 14 to facilitate the reading of the local reactions.
Rationale: Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.

Duration of exposure:

24 h, followed by an observation period of 14 days

Doses:

2000 mg/kg bw
Application volume/kg body weight: 4 mL

No. of animals per sex per dose:

Number of Animals per Group: 5 males 5 females
Total number of Animals: 5 males 5 females

Control animals:

no

Details on study design:

Observations
Viability / Mortality: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Clinical Signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.
Local Signs Once daily during days 2-15. All abnormalities were recorded.
Body Weights: On test days 1 (prior to administration), 8 and 15.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The LD50 after single dermal administration to rats of both sexes, observed over a period of 14 days

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical or local signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of the substance after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight

Executive summary:

Five male and five female HanRcc:WIST (SPF) rats were treated with the test substance at 2000 mg/kg by dermal application. The test item was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered at a volume dosage of 4 mL/kg. The application period was 24 hours.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-5. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study.

No clinical or local signs were observed during the course of the study.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were observed at necropsy.

The median lethal dose of the test item after single dermal administration to rats of both sexes, observed over a period of 14 days is LD50 (rat): greater than 2000 mg/kg body weight.