N-octylpyridin-4-amine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start date 05 March 2018, Experimental completion date 27 March 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

N-octylpyridin-4-amine

EC Number:

265-019-0

EC Name:

N-octylpyridin-4-amine

Cas Number:

64690-19-3

Molecular formula:

C13H22N2

IUPAC Name:

N-octylpyridin-4-amine

Specific details on test material used for the study:

Test Item and Supporting Information
Information as provided by the Sponsor.

Identification: N-Octyl-4-pyridinamine
Batch: 80030735B
Purity: 99.6%
Physical state/Appearance: white solid
Expiry Date: 28 November 2018
Storage Conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Animal Information
Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight of any previously treated animals.

Animal Care and Husbandry
The animals were housed in groups ofup to four in suspended solid-floor polypropylene cages furnished with wood flakes. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

The animals were provided with environmental emichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

Test Item Preparation and Analysis
For the purpose of the study the test item was freshly prepared, as required, as a suspension in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.
The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Study Design
In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
A single animal was treated as follows:
Dose Level (mg/kg): 300
Concentration (mg/mL): 30
Dose Volume (mL/kg): 30
Number of Rats: 1 Female

In the absence of mortality at a dose level of 300 mg/kg, an additional animal was treated as follows:

Dose Level (mg/kg): 2000
Concentration (mg/mL): 200
Dose Volume (mL/kg): 10
Number of Rats: 1 Female

Due to mortality at a dose level of 2000 mg/kg, an additional group of animals were treated as follows.

Dose Level (mg/kg): 300
Concentration (mg/mL): 30
Dose Volume (mL/kg): 10
Number of Rats: 4 Female

A total of five animals were therefore treated at a dose level of 300 mg/kg in the study.

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.

Doses:

2000 mg/kg bw
300 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw: 1 female
300 mg/kg bw: 5 females

Control animals:

no

Details on study design:

Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day O (the day of dosing) and on Days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

The test item was classified according to Annex 3 of the OECD Guidelines for Testing of Chemicals No. 420 "Acute Oral Toxicity - Fixed Dose Procedure" (adopted 17 December 2001) as shown in the Flow Chart in Annex 2.

Evaluation of data included identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of evident toxicity were described.
Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on body weights and abnormalities noted at necropsy were also identified.

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg - no mortality (5 females)
2000 mg/kg - 1 mortality (1 female) The animal was killed for humane reasons fifty-five minutes after dosing due to the occurrence of clinical signs of toxicity that approached the severity limit set forth in the UK Home office Project License.

Clinical signs:

other: 300mg/kg bw: Signs of systemic toxicity noted up to four days after dosing were hunched posture, ataxia, loss of righting reflex, pilo-erection, occasional body tremors, tiptoe gait, staining around the eyes and staining around the snout. 2000mg/kg bw: Si

Gross pathology:

300mg/kg bw: No abnormalities were noted at necropsy
2000mg/kg bw: Slight hemorrhage of the non-glandular region of the stomach was noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (Globally Harmonized Classification System - Category 4).
The test item was also classified as Category 4 according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures. It is reasonable to assume that the Signal Word "Warning" and the Hazard Statement
"H302: Harmful if swallowed" are therefore required.