Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 September 2009 - 31 May 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guideline; adequate coherence between data, comments and conclusions.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
The temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges specified in the study plan.
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
The temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges specified in the study plan.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:

- Chemical name: 2-[(1-methylpropyl)amino]ethanol
- Physical state: colorless liquid
- Analytical purity: 99.73%
- Impurities (identity and concentrations): EAC =0.066%, sum of unknown=0.171%, sum of organics =0.237%, water =0.035%
- Lot/batch No.: V68M010101
- Expiration date of the lot/batch: 28 January 2011
- Storage conditions of test material: at room temperature and protected from humidity

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks old
- Weight at study initiation: 200 +/- 5 g
- Fasting period before study: 18 hours
- Housing: polycarbonate cages with stainless steel lid
- Diet (e.g. ad libitum): SSNIFF R/M-H pelleted maintenance diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days before beginning ot the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 29 September 2009 To: 28 October 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
purified
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
The test item was prepared at the chosen concentrations in the vehicle.
The pH of each dosage form was measured before each treatment. The obtained values were as follows:
- 15 mg/mL (first treatment): pH = 11.58,
- 100 mg/mL: pH = 11.95,
- 15 mg/mL (second treatment): pH = 11.65.
- Concentration in vehicle: 15 or 100 mg/L, at 300 or 2000 mg/kg
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: standard vehicle used for specifie routes of administration

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to information available on the test item, for animal welfare reasons, the starting
dose-level of 300 mg/kg was chosen.
Doses:
300 and 2000 mg/kg.
No. of animals per sex per dose:
Three females per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: a period of up to 14 days
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
Type, time of onset and duration of clinical signs were recorded for each animal individually.
Time of death was recorded individually, in terms of the number of hours or days after dosing.
The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.

- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Dose-level of 300 mg/kg (three females then confirmation on three other females): no mortality.
Dose-level of 2000 mg/kg (three females): all the females were found dead 4 hours after treatment.
Clinical signs:
Dose-level of 300 mg/kg: no clinical signs were noted at this dose-level.
Dose-level of 2000 mg/kg : hypoactivity or sedation and dyspnea (all the animals), piloerection (one animal), loud breathing and hypersalivation (another animal) were observed prior to the death.
Body weight:
When compared to historical control animals, a lower body weight gain was noted in 1/6 females between day 8 and day 15. The body weight gain of the other animals was not affected by treatment with the test item.
Gross pathology:
At necropsy, a reddish discoloration of mucous membranes was observed in the stomach, intestines and liver of all the females given 2000 mg/kg.
Macroscopic examination of the main organs of the animals given 300 mg/kg revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information category 4 Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of the test item was comprised between 300 and 2000 mg/kg in rats.
Executive summary:
The acute oral toxicity of 2-[(1-methylpropyl)amino]ethanol was evaluated in rats according to OECD (No. 423, 17th December 2001) and Commission Regulation (EC) (No. 440/2008, B.1tris, 30 May 2008) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. 2-[(1-methylpropyl)amino]ethanol was prepared in purified water and was administered by oral route (gavage), under a volume of 20 mL/kg, at the dose levels of 300 and 2000 mg/kg bw to 6 or 3 fasted female Sprague-Dawley rats, respectively. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration. All animals were subjected to necropsy. Neither mortality nor clinical signs were noted at 300 mg/kg.When compared to historical control animals, a lower body weight gain was noted in 1/6 females between day 8 and day 15. At necropsy, no apparent abnormalities were observed in any animal. All the 3 females were found dead 4 hours after treatment at 2000 mg/kg. Hypoactivity or sedation and dyspnea (all the animals), piloerection (one animal), loud breathing and hypersalivation (another animal) were observed prior to the death. At necropsy, a reddish discoloration of mucous membranes was observed in the stomach, intestines and liver of all the females. The oral LD50of 2-[(1-methylpropyl)amino]ethanol was comprised between 300 and 2000 mg/kg in rats.