Octadecanoic acid, 12-hydroxy-, reaction products with ethylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 25 July 2012 to 21 September 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

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octadecanoic acid, 12-hydroxy-, reaction products with ethylenediamine

EC Number:

309-629-8

EC Name:

Octadecanoic acid, 12-hydroxy-, reaction products with ethylenediamine

Cas Number:

100545-48-0

Molecular formula:

No discrete molecular formula available for this UVCB substance

IUPAC Name:

Reaction products of 12-hydroxyoctadecanoic acid with ethane-1,2-diamine

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: Approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 207 g (range: 191 g to 225 g)
- Fasting period before study: Yes, fasted overnight before treatment. Food was given approximately 4 h after administration of the test substance.
- Housing: The animals were housed by three from the same group in polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: Tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: At least 5 or 8 d before the treatment.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 50 ± 20%
- Air changes: Approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 07 August 2012 to 05 September 2012.

DEVIATION: The temperature recorded in the animal room was sometimes outside of the target ranges specified in the study plan. However, this deviation was considered not to have compromised the validity or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methylcellulose aqueous

Details on oral exposure:

VEHICLE
The solubility assay first started at the concentration of 200 mg/mL, and the first choice vehicle was drinking water treated by reverse osmosis.
Since a heterogeneous suspension at 200 mg/mL was obtained with drinking water treated by reverse osmosis, the test substance was tested with a 0.5% methylcellulose aqueous solution.
A homogenous suspension was obtained at the concentration of 200 mg/mL in a 0.5% methylcellulose aqueous solution.

DOSAGE PREPARATION (if unusual): The test substance was administered as a homogeneous suspension in the vehicle. The test substance was ground to a fine powder, using a mortar and pestle, and then mixed with the required quantity of vehicle.
Dose formulations preparations were prepared extemporaneously on the day of each administration.
The dose formulations were stored at room temperature and delivered to the study room in brown flasks.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose:
Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose level was 300 mg/kg for ethical reasons.
After treatment at the starting dose-level, the next higher dose-level of 2,000 mg/kg was tested.

ADMINISTRATION:
The dose formulations were administered once by gavage, using a plastic syringe fitted with a plastic gavage tube. The quantity of dose formulation administered to each animal was adjusted according to the bodyweight recorded on the day of the dose administration.
A constant dosage-volume of 10 mL/kg was used. The dose formulations were stirred continuously throughout the dosing procedure.

Doses:

300 and 2000 mg/kg bw.

No. of animals per sex per dose:

3 females per treatment step.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: At least once during the first 30 minutes, periodically during the first 4 hours, then once a day, at approximately the same time.
- Morbidity and mortality: Frequently during the hours following administration, then at least once a day until the end of the observation period, including weekends and public holidays.
- Bodyweight: Just before treatment on Day 1; then on Days 8 and 15.
- Necropsy of survivors performed: Yes (macroscopic). The main organs included the digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities. All gross observations were recorded individually for each animal.

Statistics:

none

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed in any animals.

Gross pathology:

There were no macroscopic post-mortem findings.

Any other information on results incl. tables

Table 7.2.1/1: Mean body weight changes (g) in treated animals during the observation period compared to laboratory historical control data

Sex	Female
Group	Laboratory Historical control data	1	2	3
Dose-level (mg/kg bw)	0	300	2000	2000
Body weight
Day 1	219	196	206	219
Day 8	264	241	246	263
Day 15	284	256	261	274
Body weight change
Day 1	+44	+45	+40	+44
Day 8	+20	+15	+15	+11
Day 15	+64	+60	+55	+55

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the oral LD0 of the test substance was equal or higher than 2,000 mg/kg bw in rats.

Executive summary:

The substance was tested for acute oral toxicity according to the OECD 423 guideline and in compliance with Good Laboratory Practice.

The test item was administered once by gavage to 3 groups of 3 fasted female rats under a dosage-volume of 10 mL/kg bw. The test item was prepared in a 0.5% solution in methylcellulose. Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account, the starting dose-level was 300 mg/kg bw for ethical reasons. After the first assay, the next higher dose-level of 2000 mg/kg bw was tested. Since no toxicity was observed at this higher dose-level, the results were confirmed in other females.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. The bodyweight was recorded before treatment then on days 1, 8 and 15. All surviving animals were necropsied at the end of the observation period.

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals. A trend towards a slightly lower mean bodyweight gain was noted in females given the test substance at 2,000 mg/kg, when compared to historical control data. There were no macroscopic post-mortem findings.

The acute oral LD50 was found greater than 2000 mg/kg bw.