Reaction mass of 2-hexadecyl-N-(2-hydroxyethyl)-3-oxoicosanamide, 2-hexadecyl-N-(2-hydroxyethyl)-3-oxo-, N-(2-hydroxyethyl)-3-oxo-2-tetradecylicosanamide and N-(2-hydroxyethyl)-3-oxo-2-tetradecyloctadecanamide.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

study conducted between 09-Aug-2011 and 01-Sep-2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

PC-9S

IUPAC Name:

PC-9S

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: PC-9S
Description: Off-white powder
Batch Number: PS101103
Purity: Over 99%
Expiry Date: 18-11-2012

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands
- Age at study initiation: 11 weeks
- Weight at study initiation: 184.0 g – 204.3 g
- Fasting period before study: yes - overnight
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Teklad Rat-Mouse Diet 2914C, irradiated, batch no. 12/11 (ad libitum)
- Water (e.g. ad libitum): Community tap water from Itingen ad libitum.
- Acclimation period: Seven to nine days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with a room temperature of 22 ± 3 °C and a relative humidity between 30-70%, automatically controlled light cycle of 12 hours light and 12 hours dark and music played during the daytime light period.

IN-LIFE DATES: From: Day 0 To: End of Study

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
Polyethylene glycol 300 (PEG300)
Batch Number: STBB 2046M9
Supplier: Aldrich
Expiry Date: 11-Mar-2015

PEG300 was found to be a suitable vehicle. The vehicle was chosen according to sponsor’s knowledge.

DOSAGE PREPARATION:
The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle was added (weight:volume). The formulations were prepared using a magnetic stirrer as homogenizer.

DOSING VOLUME:
The dosing volume was 10 mL/kg body weight.

Doses:

2000 mg/kg

No. of animals per sex per dose:

two groups of 3 females were dosed at a concentration of 2000 mg/kg.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body Weights: On test days 1 (prior to administration), 8 and 15.
Mortality: This was checked for at the following times, Daily during acclimatization. Once before treatment and within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on test day 1 (in common with the clinical signs). Twice daily during days 2 – 15.
- Necropsy of survivors performed: yes
All animals were sacrificed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs was performed. The appearance of any macroscopic abnormalities was recorded. No organs or tissues were retained.

Statistics:

No statistical analysis was performed.

Results and discussion

Preliminary study:

No data available.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: No clinical signs were observed during the acclimation period. Three females showed slightly decreased activity on the day of treatment. No clinical signs were observed in any female on the days after test item administration.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Any other information on results incl. tables

As no effects were seen for either mortality, bodyweights, clinical signs or at necropsy, we have not included any tables.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of PC-9S after single oral administration to female rats, observed over a period of 14 days, is:

LD50 (female rat): greater than 2000 mg/kg body weight

Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), PC-9S is not classified with respect to acute oral toxicity in the rat.

Executive summary:

Two groups, each consisting of three female RccHan: WIST (SPF) rats, were treated with PC-9S by single oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in Polyethylene glycol 300 (PEG300) at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

No intercurrent deaths occurred during the course of the study. Three females showed slightly decreased activity on the day of treatment. No clinical signs were observed in any female on the days after test item administration.

The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The median lethal dose of PC-9S after single oral administration to female rats, observed over a period of 14 days, is:

LD50 (female rat): greater than 2000 mg/kg body weight.

Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), PC-9S is not classified with respect to acute oral toxicity in the rat.