Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016-05-08 - 2016-06-24 (experimental phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted: 17th December 2001
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Slovak National Accreditation Service
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-methylpiperidine-2-ethanol
EC Number:
208-554-7
EC Name:
1-methylpiperidine-2-ethanol
Cas Number:
533-15-3
Molecular formula:
C8H17NO
IUPAC Name:
2-(1-methylpiperidin-2-yl)ethanol
Test material form:
liquid
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature (20 ± 5°C); keep away from light

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Velaz Prague, Czech Republic
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 180 - 200 g
- Fasting period before study: yes, overnight
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage in a room equipped with central air-conditioning. Bedding was Lignocel S3/4, Lufa - ITL GmbH, Germany
- Diet (e.g. ad libitum): A laboratory food Altromin (Altromin Spezialfutter GmbH, Germany) was offered in recommended doses each day approximately at the same time.
- Water (e.g. ad libitum): The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodical analysed (including microbiological control) and recorded.
- Acclimation period: The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2° C
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 12-hour light /12-hour dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Olive Oil is a standard vehicle according to OECD TG 423
- Lot/batch no. (if required): L52897

DOSAGE PREPARATION (if unusual):
The required amount of the Test Item (according to the body weight and dose) was mixed with vehicle (Olive Oil) shortly before administration.
Doses:
2000, 300 mg/kg bw
No. of animals per sex per dose:
3 females for the 2000 mg/kg dose, 6 females for the 300 mg/kg dose
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually immediately after the administration of the Test Item and then 0.5, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Individual weights of animals were determined shortly before the Test Item was administered and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.
- Necropsy of survivors performed: Yes. All test animals were subjected to gross necropsy. Full, detailed gross necropsy included careful examination of external surface of the body, all orifices, and cranial, thoracic and abdominal cavities and their contents. All gross pathological changes were recorded for each animal.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg of OECD Guideline 423 it can be concluded that the Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) is classified in Category 4 with a LD50 cut off value 500 mg/kg.
Sex:
female
Dose descriptor:
LD100
Effect level:
<= 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD0
Effect level:
>= 300 mg/kg bw
Based on:
test mat.
Mortality:
Mortality of all 3/3 females at limit dose of 2000 mg/kg was noted. All 6/6 females survived the dose of 300 mg/kg.
Clinical signs:
Half an hour after treatment with the limit dose of 2000 mg/kg animals were sleepy and lethargic. This behaviour was observed also after 1 and 2 hours. At the next control time point (4 hours), all animals were found dead. Time of animals death was between 2-4 hours after administration of the Test Item.
No mortality was observed in females treated with the Test Item in dose of 300 mg/kg. Five of six animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered. One of six females was sleepy and lethargic from day 3 to the end of the observation period.
Body weight:
The body weights of 5 animals treated with the dose of 300 mg/kg were increasing during the study. No body weight losses were observed first and second week after administration. The one exception was the rat No 9. Body weight decrease after week 1was 50 g and after week 2 another 10 g. Total decrease of body weight was 60 g against initial value.
Gross pathology:
All animals were necropsied. During necropsy, marked enlargement of adrenals were noticed in 3/3 animals treated with dose of 2000 mg/kg.
In 2/6 animals treated with dose of 300 mg/kg moderate enlargement of adrenals and a marked bloating in all intestine segments in one animal were registered. No macroscopic changes were noticed in 3/6 animals.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The study was conducted under GLP according to OECD guideline 423 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation or any deviations. Hence, the results can be considered as reliable to assess the acute toxicity of 2-(1-methylpiperidin-2yl) ethanol, (MPA) in rats.
The Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) administered to 3 females at dose of 2000 mg/kg caused sleepiness, lethargy and finally death of all animals within 2 - 4 hours after treatment. During necropsy, marked enlargement of adrenals was found.
The Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) administered to 6 females at dose of 300 mg/kg did not cause death.
Hence, it can be concluded that the LD50 of the Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) is higher than 300 mg/kg and lower than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg of OECD Guideline 423 it can be concluded that the Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) is classified in Category 4 with a LD50 cut-off value 500 mg/kg, after single oral administration to Wistar rats.
Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. A limit dose of 2000 mg/kg was used as a starting dose. One group of 3 females was dosed. The Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) administered to 3 females at dose of 2000 mg/kg caused sleepiness, lethargy and finally death of all animals within 2 - 4 hours after treatment. The necropsy showed marked enlargement of adrenals.

Because test item-related mortality was observed during the first 4 hours, in the next 2 steps, 6 females were treated with the dose of 300 mg/kg. All 6 females survived this dose. The Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) administered to 6 females at dose of 300 mg/kg did not cause death. No body weight losses were observed in 5/6 females one and two weeks after administration of the Test Item. No signs of toxicity were observed in 5/6 females during the first 4 hours or the subsequent 14-day observation period. During necropsy moderate enlargement of adrenals in 2/6 animals and in 1/6 animal marked bloating in all intestine segments were noticed. No macroscopically changes were found in 3/6 animals.

The LD50 of the Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) is higher than 300 mg/kg and lower than 2000 mg/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg of OECD Guideline 423 it can be concluded that the Test Item 2-(1-methylpiperidin-2yl) ethanol, (MPA) is classified in Category 4 with a LD50 cutoff value 500 mg/kg, after single oral administration to Wistar rats.