Fatty acids, coco, tetraesters with bis[2,2-bis(hydroxymethyl)butyl] adipate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

between 20 May 2009 and I0 June 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in accordance with recognised guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

yes

Remarks:

Not considered to affect study validity

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

yes

Remarks:

Not considered to affect study validity

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,6-bis({2,2-bis[(undecyloxy)methyl]butyl}) hexanedioate

EC Number:

700-772-5

Cas Number:

1190961-28-4

Molecular formula:

N/A - too complex

IUPAC Name:

1,6-bis({2,2-bis[(undecyloxy)methyl]butyl}) hexanedioate

Details on test material:

- Physical state: Amber liquid
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

other: 92-93%

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 180-201 g. The bodyweight variation did not exceed 20% of the initial mean bodyweight of any previously dosed animal(s).
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: Suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 25°C
- Humidity (%): 30 – 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light/dark.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Bidistilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/ml and 200 mg/ml
- Amount of vehicle (if gavage): calculated to individual animal fasted bodyweight at time of dosing
- Justification for choice of vehicle: 10 ml/kg
- Lot/batch no. (if required): NDA
- Purity: NDA

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

total was 6 females (one animal at 300 mg/kg and five at 2000 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs observed daily, body weights measured on days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight no further details available

Statistics:

An estimate of the acute oral median lethal dose (LD50) of the substance was made using the mortality data obtained.

Results and discussion

Preliminary study:

Asingle female rat was dosed at a level of 300 mg/kg bw.
There was no mortality.
Asingle female rat was dosed at a level of 2000 mg/kg bw.
There was no mortality.

As such, an additional group of 4 animals were dosed at 2000 mg/kg in the main study.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

- Organ weights: No Data Available
- Histopathology: No Data Available
- Potential target organs: No Data Available
- Other observations:No Data Available

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female RccHan:WIST strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonized Classification System -Unclassified).

Executive summary:

INTRODUCTION

The study was performed to assess the acute oral toxicity of the test material in the RccHan:WIST strain rat. The method was designed to meet the requirements of the following:

OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity -Fixed Dose Method" (adopted 17 December 2001)

Method B1 Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

METHODS

To determine the dose level for the main study, two sighting studies were conducted with one animal each (female RccHan:WIST (SPF) rat). The two animals were treated sequentially with the test item at the dose levels of 300 or 2000 mg/kg body weight by single oral gavage administration. The test item was formulated in purified water at a concentration of 0.03 g/mL and 0.2 g/mL, respectively and administered at a dose volume of 10 mL/kg. Since no mortality occurred in the animal treated with 2000 mg/kg body weight, additional four females were treated at this dose level in the main study.

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 test 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 test days 2-15. Body weights were recorded on test day 1 (prior to administration) and on test days 8 and 15. All animals were necropsied and macroscopically examined.

RESULTS

Mortality: There were no deaths.

Clinical Observations: On the day of the treatment, the animal treated with 300 mg/kg body weight showed ruffled fur up to three hours after application. Thereafter no clinical signs were observed. All five animals treated with 2000 mg/kg body weight did not show any clinical signs after treatment.

Body weight: The body weight of the animals was within the range commonly recorded for this strain and age.

Necropsy: No abnormalities were noted at necropsy.

CONCLUSION

The LD50 after single oral administration to female rats, observed over a period of 14 days, is 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), the test substance is not classified with respect to acute oral toxicity in the rat.