7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 May 1999 - 9 September 1999.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary guideline study conforming to the relevant guidelines.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

1

Reference substance name:

Cycloaliphatic Epoxy Resin ERL-422 1

IUPAC Name:

Cycloaliphatic Epoxy Resin ERL-422 1

Specific details on test material used for the study:

- Name of test material (as cited in study report): Cycloaliphatic Epoxy Resin ERL-4221

- Substance type: Not documented
- Physical state: Clear, colorless, viscous liquid
- Analytical purity: Not documented
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Certificate of Analysis dated 2 October 1999
- Lot/batch No.: 87068
- Expiration date of the lot/batch: Not documented

- Stability under test conditions: Test article stability data are being monitored as part of the test program and will be reported separately.
- Storage condition of test material: Original container at room temperature

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: Eight to nine weeks old (males) and nine to 10 weeks old (females)
- Weight at study initiation: 264 to 299 g (males) and 200 to 228 g (females)
- Fasting period before study: Food was withheld during the 18- to 20-hour period immediately prior to dosing and returned three to four hours after dosing.
- Housing: Individually in suspended wire-mesh cages.
- Diet (e.g. ad libitum): PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 ad libitum
- Water (e.g. ad libitum): Reverse osmosis treated municipal water
- Acclimation period: Minimum of seven days prior to initiation of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8 - 22.3°C
- Humidity (%): 43.3-62.4%
- Air changes (per hr): Not documented
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: May 21, 1999 To: June 11, 1999

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Not applicable
- Amount of vehicle (if gavage): Not applicable
- Justification for choice of vehicle: Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable

MAXIMUM DOSE VOLUME APPLIED: The dose volume was determined by dividing the dose levels of 2959 and 5000 mg/kg, by the specific gravity (1180 mg/mL). Individual doses of the test article were calculated based on body weights obtained just prior to dosing and dose levels of 2.51 and 4.24 ml/kg for the 2959 and 5000 mg/kg groups, respectively.

DOSAGE PREPARATION (if unusual):
A sufficient amount of test article, agitated prior to use, was transferred from the original container to a labelled storage container. A stir bar was added, and the test article was stirred continuously throughout use.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not applicable

Doses:

2959 and 5000 mg/kg

No. of animals per sex per dose:

20 animals (10 male and 10 female)
Groups of five male and five female were administered either 2959 or 5000 mg/kg dose levels.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed at approximately 1, 3 and 4 hours post-dosing on day 0 and once daily thereafter for 14 days. Body weights were obtained and recorded on study days -1, 0 (initiation), 7 and 14 (termination). In addition, decedents were weighed as soon as they were found.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight; other: The major organ systems of the cranial, thoracic and abdominal cavities were examined for all animals.

Statistics:

No information provided.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 959 - < 5 000 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Three males and two females died within six days of dosing. Mortality was 0/10 and 5/10 for the 2959 and 5000 mg/kg groups, respectively. Single deaths occurred on days 2, 3, 4, 5 and 6.

Clinical signs:

other: other: Clinical findings were noted in both dose groups during the first week of the study. Four animals in the 2959 mg/kg group and all animals in the 5000 mg/kg group were noted with various discolored areas due to discharges/excretions [described as w

Gross pathology:

Three animals (one male and two females) that died were noted with dark red contents in the stomach and/or a distended stomach. Various red and/or yellow matting around the eyes, nose, anogenital and/or urogenital area was noted for these animals that died. There were no other necropsy findings for animals found dead. One male from the 5000 mg/kg group was noted with capsular scarring of the spleen at the scheduled necropsy. There were no other findings for any examined tissues at the scheduled necropsy.

Other findings:

No additional information

Any other information on results incl. tables

No additional information

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The results of this study indicate that the LD50 of Cycloaliphatic Epoxy Resin ERL-4221 was found to be approximately 5000 mg/kg in fasted male and female albino rats when administered once orally via gavage. Based on these results, it was not necessary to classify the test substance according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Executive summary:

In a study conducted by Kern (1999), the acute oral toxicity of Cycloaliphatic Epoxy Resin ERL-4221 was evaluated in a single-dose study in rats. The test article was administered once orally via gavage to groups of five male and five female fasted albino rats at dose levels of 2959 and 5000 mg/kg. The animals were observed at regular intervals for up to 14 days following administration to ascertain any changes in body weight or clinical behaviour. At termination of the study after 14 days, the animals were necropsied and any changes in the major organs was recorded.

3 males and 2 females in the 5000 mg/kg group died within six days of dosing. Mortality was 0/10 and 5/10 for the 2959 and 5000 mg/kg groups, respectively. Clinical findings were noted in both dose groups during the first week of the study with observations including various discolored areas due to discharges/excretions, hypoactivity and/or impaired muscle coordination. Animals in the higher dose group were noted with decreased defecation, decreased urination, labored respiration and/or convulsions. All animals appeared normal by day 6 and throughout the remainder of the study. Three animals that died were noted with gastric abnormalities. There were no other internal gross necropsy findings for animals found dead.

The LD₅₀ of Cycloaliphatic Epoxy Resin ERL-4221 was found to be approximately 5000 mg/kg in fasted male and female albino rats

when administered once orally via gavage. Since the median lethal dose estimate was much higher than the test guideline limit, it was not necessary to classify the test substance according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.