Reaction products of 12-hydroxyoctadecanoic acid with ethane-1,2-diamine and hexane-1,6-diamine and 1,3-phenylenedimethanamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2012-07-19 to 2012-11-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 12-hydroxyoctadecanoic acid with ethane-1,2-diamine and hexane-1,6-diamine and 1,3-phenylenedimethanamine

EC Number:

700-825-2

Molecular formula:

Not applicable (UVCB substance).

IUPAC Name:

Reaction products of 12-hydroxyoctadecanoic acid with ethane-1,2-diamine and hexane-1,6-diamine and 1,3-phenylenedimethanamine

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: 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: 217 g (range: 202 g to 227 g)
- Fasting period before study: yes, during the night before treatment
- 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 days before the beginning of the study.

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

IN-LIFE DATES: 04 September 2012 to 04 October 2012.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/ml
- Justification for choice of vehicle: The vehicle used in this study was selected from the results of solubility assays. The solubility assay first started at the concentration of 200 mg/mL, and the first choice vehicle was drinking water treated by reverse osmosis. As unsatisfactory solubility of the test item was obtained in this vehicle (i.e. heterogeneous preparation at the concentration of 200 mg/mL was obtained), another vehicle was chosen from the following organic solvents (in order of preference): 0.5% methylcellulose aqueous solution and corn oil. A homogenous suspension was obtained at the concentration of 200 mg/mL in corn oil.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

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, the starting dose level was 300 mg/kg for ethical reasons.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 per treatment step.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment, then on day of treatment (day 1) and on days 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

none

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

Piloerection was observed in 3 out of 6 females given 2000 mg/kg bw 4 hours after treatment on day 1 and on day 2.
No clinical signs were observed in other animals.

Body weight:

A slightly lower body weight gain was noted in one or two females per group (30 g to 37 g vs. 44 g ± 4.2 g in control data base) between day 1 and day 8. A lower body weight gain was also noted in one or two females per group (3 g to 10 g vs. 20 g ± 5.7 g in control data base) between day 8 and day 15.
When considering the day 1 to day 15 period, the body weight change was lower in two females from group 1 treated at the dose-level of 300 mg/kg (40 g and 45 g) and in 4/6 females treated at the dose-level of 2000 mg/kg (between 49 g and 57 g).

Gross pathology:

No abnormalities were noted.

Other findings:

None

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	225	218	210
Day 8	264	264	254	253
Day 15	284	273	270	269
Body weight change
Day 1	+44	+39	+36	+43
Day 8	+20	+10	+16	+16
Day 15	+64	+48	+52	+60

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 of the test substance was higher than 2000 mg/kg in rats.
Therefore, the substance is not classified according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures.

Executive summary:

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

 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 corn oil. Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data have been 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. Then, as 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. Body weight 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.

Piloerection was observed in 3 out 6 females given 2000 mg/kg bw 4 hours after treatment on day 1 and on day 2. No clinical signs were observed in other animals.

When compared to laboratory historical control data, a slightly lower body weight gain was noted in one or two females per group between day 1 and day 8 and between day 8 and day 15. When considering the day 1 to day 15 period, the body weight change was lower in two females treated at the dose-level of 300 mg/kg bw and in 4 out of 6 females treated at the dose-level of 2000 mg/kg bw compared to laboratory historical control data.

At necropsy, there were no macroscopic findings related to the test item administration.

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