4-(1-piperidinyl)-2-(E)-butenoicacid hydrochloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23rd August 2011 to 26th January 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 4

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

1-[(2E)-3-carboxyprop-2-en-1-yl]piperidin-1-ium chloride

EC Number:

690-933-5

Cas Number:

197892-69-6

Molecular formula:

C9H16ClNO2

IUPAC Name:

1-[(2E)-3-carboxyprop-2-en-1-yl]piperidin-1-ium chloride

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant
- Age at study initiation: approx. 11-12 weeks old
- Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage enrichment.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3 – 21.9
- Humidity (%): 40 - 59
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: To: 9th November 2011 to 29th November 2011

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

Single dosage on Day 1.
2000 mg/kg (10 mL/kg) body weight

No. of animals per sex per dose:

Three

Details on study design:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines.
The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality occurred

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of PF-00818977-01 in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

Assessment of acute oral toxicity with PF-00818977-01 in the rat (Acute Toxic Class Method).
The study was carried out based on the guidelines described in:
OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"
Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method"
EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"
JMAFF guidelines (2011) including the most recent partial revisions.

PF-00818977-01 was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).
No mortality occurred.
Hunched posture, piloerection, salivation and/or shallow respiration were noted in all animals on Day 1.
The body weight gain shown by the animals over the study period was considered to be normal.
No abnormalities were found at macroscopic post mortem examination of the animals.
The oral LD50 value of PF-00818977-01 in Wistar rats was established to exceed 2000 mg/kg body weight.
Based on these results, PF-00818977-01 does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.