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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not applicable
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline 401.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ethyl-3-Ethoxypropionate
- Substance type:
- Physical state: liquid
- Analytical purity: 99.9% by Gas chromatography with flame ionization detection methodology.
- Purity test date: no data
- Lot/batch No.: X-18626-184-6
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:
rat
Strain:
other: CRL: CD® (SD)BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA, U.S.A.
- Age at study initiation: approximately 7-9 weeks old
- Weight at study initiation: Males: 216-246 g; Females: 182-198 g.
- Fasting period before study: Yes. Overnight
- Housing: All animals were individually housed in suspended stainless steel mesh cages
- Diet: Agway Prolab® Animal Diet (RMH 3000) certified pellet s were fed ad libitum.
- Water: Water was supplied ad libitum through an automatic watering system.
- Acclimation period: Rats were quarantined and monitored for at least 5 days after arrival before release to the testing facility.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.7-22.8
- Humidity (%): 38- 52%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours from 6 a.m. to 6 p.m.


IN-LIFE DATES: From: 5 May 1986 To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
A single dose was administered by gavage to animals that had been fasted overnight.

Doses:
limit dose: 5000 mg/kg BW
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed several times during the first 24 hours after dosing and once each workday thereafter for the duration of the test (a total of 14 calendar days). Body weights were collected on the day of dosing and one and two weeks after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: Observation included, but was not limited to, examination of the hair, skin, eyes, motor activity, feces and urine. Animals were checked for mortality on weekends.
Statistics:
Not applicable

Results and discussion

Preliminary study:
In a preliminary study no mortality was observed in females administered doses up to 3200 mg/kg bw.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
4 309 mg/kg bw
95% CL:
2 781 - 6 677
Remarks on result:
other: calculated based on results of this study and a preliminary study with doses up to 3200 mg/kg bw.
Mortality:
males: 0/5 died at 5000 mg/kg bw
females: 3/5 died at 5000 mg/kg bw (in a previous study 0/5 died at 3200 mg/kg bw)
Clinical signs:
All animals demonstrated slight weakness and ataxia on the day after dosing (Day 1). On Day 2 and all subsequent days, no abnormal clinical signs were observed. Females: No abnormal clinical signs were observed on the day of dosing, but two animals were found dead in the morning of the next day, at which time the three remaining animals demonstrated moderate to severe weakness and ataxia. A third animal died during the night between Days 1 and 2. On Day 2, the two remaining animals had slight weakness, but were clinically normal on Day 3. On all subsequent days, no abnormal clinical signs were observed in the remaining animals.
Body weight:
All seven surviving animals demonstrated weight gain at one and two weeks after dosing.
Gross pathology:
Petechial hemorrhage was observed in the gastric mucosa of the female rats which died on Test days 1. Minimal red discoloration of the pancreas, due to congestion, was observed in the rat that died on Test day 2. The perianal hair ofthis rat was discolored yellow due to fecal staining. Gastric petechial hemorrhage was interpreted as indicating irritation of the stomach lining. Pancreatic and hair staining were considered non-specific effects secondary to test article exposure. Moderate hemorrhage in the thymus of the rat from Test day 2 was considered an agonal lesion associated with the death process rather than toxicity. Focal pneumonitis commonly occurs in untreated rats and was not considered related to test article exposure.
Other findings:
- Organ weights: not conducted
- Histopathology: Lesions related to test article exposure were not found in any of the rats surviving the 14-day observation period.
- Potential target organs:
- Other observations: A small number of non-specific lesions related to test article exposure were found in the rats that died on Test day 1 or2. These included mucus in the tracheal lumen, thymic hemorrhage, cardiac hemorrhage, renal vascular congestion, adrenal gland vascular congestion, pancreatic vascular congestion, contraction of the spleen, and cerebral vascular congestion. All of these lesions were considered agonal or associated with the death process and not related to toxicity. None of the lesions were considered significant contributory factors in the deaths of these 3 female rats. Other lesions, including inflammatory lesions observed in the trachea, lungs, liver and kidneys, were considered incidental and unrelated to test article exposure.

Any other information on results incl. tables

The cause of deaths in three female rats was not evident from the pathology data, but there was no evidence of significant organ damage after extensive tissue analysis. This finding is consistent with deaths caused by anesthesia following exposure to high levels of solvents. There was no evidence of specific neurotoxicity following examination of the brain, spinal cord, peripheral nerves, dorsal root ganglia, skeletal muscle, and neural tissue present in visceral organs.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Cassified as slightly toxic in females and practically non-toxic i n males by the oral route. Criteria used for interpretation of results: EU
Conclusions:
The LD50 in males was greater than 5000 mg/kg, based on the survival of all five animals given that dose. The LD50 in females is calculated to be 4309 mg/kg bw.
Executive summary:

A single dose of 5000 mg/kg bw was administered to rats by oral gavage. None of the male rats died at this dose level and the LD50 for male rats can be established to be greater than 5000 mg/kg bw.

For female rats 3/5 died at 5000 mg/kg bw. However, in a previous study (see TX 83 -70) dose levels of 1600 and 3200 mg/kg bw were administered to female rats and 0/4 animals died at both dose levels. Based on the results of the two studies and LD50 of 4309 mg/kg bw was calculated for female rats.