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

Endpoint summary

Description of key information

Acute oral LD50 between 300 and 2000 mg/kg bw, with a cut-off of 500 mg/kg bw. Acute dermal and inhalation toxicity have not been evaluated following the corrosive properties and the very low vp of the pasty substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

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

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

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).

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Quality of whole database:

According to GLP and recent guidelines.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

The acute oral toxicity was evaluated by Acute Toxic Class method (OECD 423).Groups of three female Wistar rats were dosedOleyl-diamine mono-oleateby oral gavage in a volume of 10 mL/kg bw propylene glycolThe 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.

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

 

Acute dermal toxicity:

There is no dermal LD 50 value for acute skin toxicity of Oleyl-diamine mono-oleate, and due to the corrosive properties combined with relative low oral toxicity of the substance, it is not ethical to carry out this animal study.

 

Acute inhalation toxicity:

There is no study on inhalation toxicity available for Oleyl-diamine mono-oleate.

REACH stipulates that testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. REACH guidance R.7.a, chapter. 7.4 Acute toxicity indicates that in principle no inhalation studies are needed when vp < 0.1 Pa at 20°C or particle size > 100 µm. Oleyl-diamine mono-oleate a paste with a vapour pressure of ≤ 0.00087 Pa at 25 °C. Its use is limited to industrial and professional users and does not involve the forming of aerosols, particles or droplets of an inhalable size. So exposure to humans via the inhalation route will be unlikely to occur.

 

No information on viscosity is available at 40°C, and hence the hazard for aspiration cannot be adequately assessed.

Justification for classification or non-classification

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

The substance therefore need to be classified under CLP for acute oral toxicity asCategory 4, with H302: Harmful if swallowed.

Dermal systemic toxicity is expected to be low, while corrosive properties will limit likelihood of exposures.

Related to low vp and no inhalable particles, there will be low likelihood of exposures via inhalation.

No classification STOT-SE Cat.3 needed:

The active substance is not structurally related to any known class of neurotoxic chemicals.