Oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 June 2018 - 05 July 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

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)

Version / remarks:

November 2000, including the most recent revisions

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine

EC Number:

254-754-2

EC Name:

Oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine

Cas Number:

40027-38-1

Molecular formula:

C21H44N2xC18H34O2

IUPAC Name:

oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine

Test material form:

solid

Details on test material:

Substance Name: N-(Oleyl alkyl)- 1,3-propanediamine mono oleate
CAS: 40027-38-1
Lot/Batch: P15-005
Appearance: Yellow paste at 20°C
Test item storage: At room temperature
Date of Production: 2015-02-18
Best before Date: 2020-02-18
Trade Name: Armolube 211
mp 30-40°C 
D = 880 kg/m³ at 40°C 
m.form. C39H78N2O2
mw 607.065
Purity: UVCB
Purity test date: 24 April 2018

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adult animals of approx. 9-10 weeks old
- Weight at study initiation: 155 to 185 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Group housing of 3 animals per cage in polycarbonate cages (MIV type; height 18 cm.), containing sterilized sawdust as bedding material and paper as cage-enrichtment.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 18-24 (actual: 21-22)
- Humidity (%): 40-70 (actual: 32-72) - this deviation is considered not to have affected the integrity of the study because it did not noticeably affect the clinical condition of the animals or the outcome of the study.
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05 June 2018 - 05 July 2018

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Remarks:

Specific gravity: 1.036

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION:
- The dosing formulations were stirred continuously during administration.

CLASS METHOD:
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

The study was conducted in a stepwise manner with four groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. Based on the results, the second group was dosed at 2000 mg/kg two days after the first group based on the absence of severe tox signs. Based on results, two additional groups were dosed at 300 mg/kg.

No. of animals per sex per dose:

12 females (3 animals/dose group)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
*Mortality/Viability: twice daily;
*Body weights: on the day of dosing (fasted weight) and on days 1 (pre-administration), 8 and 15;
*Clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

The LD50 cut-off value was established based on OECD guideline 423. No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

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:

- At 2000 mg/kg, four animals were killed in extremis on Day 6 and one animal was found dead on day 7.
- At 300 mg/kg, no mortality occurred.

Clinical signs:

other: - At 2000 mg/kg, for the first dose group, hunched posture and piloerection were noted between days 1 and 3. In addition, lethargy, hunched posture, piloerection, chromodacryorrhoea, lean appearance and/or ptosis were noted prior to sacrifice on day 6. At

Gross pathology:

General emaciation, abnormalities of the stomach (irregular surface of the forestomach) and adrenal glands (both sides enlarged) and yellowish watery-cloudy contents of the jejunum,
ileum and caecum were found in three out of five animals that died or were sacrificed for humane reasons during the study, at macroscopic post mortem examination. Macroscopic
post mortem examination of the other animal that was sacrificed during the study and of the surviving animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Classified Category 4 according to Regulation (EC) No. 1272/2008

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, the LD50 of N-(Oleyl alkyl)-1,3-propanediamine mono oleate was established to be within the range of 300-2000 mg/kg body weight, with a cut-off of 500 mg/kg bw.

Executive summary:

Acute oral toxicity of N-(Oleyl alkyl)-1,3-propanediamine mono oleate was evaluated in an OECD 423 (Acute Toxic Class Method)study, performed under GLP.

Dosing was done by oral gavage to groups of three female Wistar rats in a volume of 10 mL/kg bw propylene glycol. The first group was dose at 2000 mg/kg body weight. In a stepwise procedure three additional groups of three females were dosed at 2000, 300 and 300 mg/kg body weight.

Mortality: At 2000 mg/kg, four animals were killed in extremis on day 6 and one animal was found dead on day 7. in the first three animals, 2 were sacrificed on day 6, and one was found 1 dead day 7. From the second three animals that were already dosed in the mean-time, 2 were sacrificed day 6 and one survived until end of observation period. At 300 mg/kg, no mortality occurred. Severe effects were observed at clinical observations 2000 mg/kg bw, especially prior to sacrifice. At 300 mg/kg, hunched posture, uncoordinated movements and/or piloerection were noted for the animals between Days 1 and 6.

Macroscopic Findings involved general emaciation, abnormalities of the stomach, enlarged adrenal glands and yellowish watery-cloudy contents of the intestines were found in four out of five animals that died or were sacrificed. Macroscopic post mortem examination of the other animal that was sacrificed during the study and of the surviving animals at termination did not reveal any abnormalities.

Regarding dosing a second group at 2000 mg/kg: the second group was dosed two days after the first group based on the absence of severe tox signs. Unfortunately delayed toxicity resulting in death was noted for the animals after dosing the second group.

The LD50 is concluded to be between 300 and 2000 mg/kg bw, with a cut-off of 500 mg/kg bw.