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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:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Name: Ethanol, 2,2'-oxybis-, reaction products with ammonia, morpholine derivs. residues
Physical state: liquid
Appearance: brown liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): amine C-8
- Substance type: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley or any acceptable USDA source
- Age at study initiation: 8-12 weeks at start of dosing
- Weight at study initiation: Male: 175-300 grams; female: 150-250 grams
- Fasting period before study: 18-24 hours prior to test article administration
- Housing: Animals will be housed (group housed by sex upon receipt, individually housed upon assignment to study) in compliance with the National Research Council "Guide for the Care and Use of Laboratory Animals". Calvert is a USDA registered and fully AAALAC accredited facility. The room in which the animals will be kept will be documented in the study records. No other species will be kept in the same room.
- Diet (e.g. ad libitum): All animals will have access to Harlan Teklad Rodent Diet (certified) or an equivalent certified diet ad libitum. The lot number(s) and specifications of each lot used are archived in the facility records at Calvert. No contaminants are known to be present in the certified diet at levels that would be expected to interfere with the results of this study. Analysis of the diet was limited to that performed by the manufacturer, records of which will be maintained in the Calvert archives.
- Water (e.g. ad libitum): Tap water will be available ad libitum, to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert's SOPs. No contaminants are known to be present in the water at levels that would be expected to interfere with the results of this study. Results of the water analysis will be maintained in the Calvert archives.
- Acclimation period: Study animals will be acclimated to their housing for a minimum of five days prior to their first day of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 26 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: No data

Administration / exposure

Route of administration:
oral: gavage
Details on oral exposure:
Prior to the main assay, a dose range finding study (non-GLP) is performed using one male and one female rat per dose level. Three dose levels selected by the Sponsor are administrated to the animals. The procedures follow the main assay, but the length of study is 72 hours. After review of the dose range results, groups of 5 males and 5 females will be added in a step-like manner depending on the results of each previous dose level.
Doses:
1000, 2000, 5000 mg/kg bw
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:
mortality/morbidity: once daily from days 1 to 15, each animal is observed per Calvert SOP VET-14
clinical observations: clinical observations for any toxicological signs are recorded immediately after dosing, at 0.5, 1 and 4 hours post-dose on Day 1 and once daily thereafter through Day 15
body weight: Animals are weighed prior to dosing on Day 1 (fasted) and on Days 8 and 15
- Necropsy of survivors performed: yes
Statistics:
Parameters: body weights
Method: Raw data are summarized using descriptive statistics (mean and standard deviations). When necessary, additional analysis will be performed at the request of the Study Director. Additional analysis will be performed when necessary to augment the standard analysis.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
1000 mg/kg bw/d: 0/10
2000 mg/kg bw/d: 0/10
5000 mg/kg bw/d: 5/10 (1 male, 4 females)
Clinical signs:
No clinical signs were observed in groups dosed 1000 or 2000 mg/kg bw/d. In the highest dose group, the following clinical signs were observed: decreased body tone (10/10 animals), brown discolored fur around eyes (2/10), piloerection (2/10), abnormal gait and stance (3/10), dischard (clear) eye (1/10), decreased activity (1/10). Three animals were found dead on the second day after exposure. One animal was found day on day 3.
Body weight:
No effects on body weight were observed.
Gross pathology:
No visible lesions were seen at 1000 and 2000 mg/kg bw/day. In the animals that were found dead on day 2 and 3 after exposure, following lesions were found: distended stomach, red to black fluid filled, dark lesions in stomach

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the mortalities observed after dosing 1000, 2000 or 5000 mg/kg bw/d (single dose, oral gavage), it is concluded that the LD50 is 5000 mg/kg bw/d.