Oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine (2:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 Oct 2003 - 10 Dec 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well reported and carried out study according to guidelines/standards of 1996 instead of 2001 using class 200 mg/kg rather than 300 mg/kg.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

version of 1996 rather than 2001 used

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine (2:1)

EC Number:

251-846-4

EC Name:

Oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine (2:1)

Cas Number:

34140-91-5

Molecular formula:

C21H44N2.2C18H34O2

IUPAC Name:

oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine (2:1)

Test material form:

liquid: viscous

Details on test material:

Chemical registery number : CAS 34140-91-5 / EC 251-846-4
Chemical name : N-[(9Z)-octadec-9-en-1-yl]propane-1,3-diaminium di[(9Z)-octadec-9-enoate

Based on the qualitative and quantitative information on the composition, the sample used are representative of the boundary composition shared and agree by each registrant.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
rat, Sprague-Dawley Rj: SD (IOPS Han).
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 281 ± 7 g for the males and 215 ± 8 g for the females
- Fasting period before study: approx. 18 hours until 4 hours after administration
- Housing: polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and three rats of the same sex and group during the treatment period. Each cage contained autoclaved sawdust (SICSA, Alfortville, France).
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 9 Oct 2003 To: 10 Dec 2003

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 mg/mL (200 mg/kg bw) and 200 mg/mL (2000 mg/kg bw)
- Amount of vehicle (if gavage): 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 200 mg/kg was chosen.

Doses:

200 and 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: frequently during the hours following administration and thereafter at least once per day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight on day 1, 8 and 15 , macroscopic necropsy examination

Statistics:

Not applicable in ATC

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off level according to OECD 423

Mortality:

At the 200 mg/kg dose-level, no mortality occurred.
At the 2000 mg/kg dose-level, no mortality occurred in males. In females, 1/3 animals died on day 2 and another one was found dead on day 8

Clinical signs:

other: At the 200 mg/kg dose-level piloerection and dyspnea were observed in all females on day 1, whereas no clinical signs were noted in males. At the 2000 mg/kg dose-level in males hypoactivity and dyspnea were recorded in all males on day 1. Then dyspnea, pi

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Any other information on results incl. tables

The report concluded to: Under our experimental conditions, the oral LD50 of the test item is:

- higher than 2000 mg/kg in male rats,

- comprised between 200 and 2000 mg/kg in female rats.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

An acute oral toxicity study according to OECD 423 resulted to a LD50 between 200 -2000 mg/kgbw with LD50 cut-off value of 2000 mg/kgbw.

Executive summary:

In an OECD 423 study under GLP, Oleyl-diamine dioleate (Inipol 002) was administered to groups of 3 male and 3 female rats at dose levels of 200 and 2000 mg/kgbw formulated into corn oil applied at 10 ml/kg bw. At the 200 mg/kg dose-level, no mortality occurred. Piloerection and dyspnea were observed in all females on day 1, whereas no clinical signs were noted in males.

At the 2000 mg/kg dose-level, no mortality occurred in males. Hypoactivity and dyspnea were recorded in all males on day 1. Then dyspnea, piloerection and hypoactivity were observed in 1/3 males up to day 3, 4 or 5, respectively. In females, 1 animal died on day 2 and another one was found dead on day 8; hypoactivity, piloerection and dyspnea, together with rhinorrea and ocular secretion in the last one, were noted prior to death. In the surviving female, hypoactivity, piloerection and dypnea, together with loud breathing on days 1 and 3 and rhinorrea on days 5 and 6, were recorded from day 1 up to day 8.

At necropsy, no apparent abnormalities were observed.

The report concluded that the LD50 was higher than 2000 mg/kg in male rats, and between 200 and 2000 mg/kg in female rats. OECD 423 evaluation criteria indicate LD50 between 200 -2000 mg/kgbw with LD50 cut-off value of 2000 mg/kgbw.