Octadecanedioic acid, 1,18-dimethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,18-dimethyl octadecanedioate

EC Number:

604-582-2

Cas Number:

1472-93-1

Molecular formula:

C20H38O4

IUPAC Name:

1,18-dimethyl octadecanedioate

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Octadecanedioic acid, 1,18-dimethyl ester (ODDAME)
- Physical state: white solid
- Analytical purity: 98.8 %
- Lot/batch No.: 1091-4-B
- Date received: 2011-12-12
- Storage condition of test material: room temperature in the dark
- Stability under storage conditions: analyses showed stability of the test material over the period it was stored

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK
- Age at study initiation: 8-12 weeks
- Fasting period before study: Overnight immediately prior to dosing and 3-4 hours after dosing
- Housing: Groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Free access to 2014C Teklad Global Rodent Diet supplied by Harlan Laboratories UK Ltd, Oxon, UK
- Water: Free access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 ºC
- Humidity: 30 to 70 %
- Air changes: At least 15 changes per hour
- Photoperiod: 12 hours light (06:00 to 18:00) and 12 hours dark controlled by a time switch

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Arachis oil BP

Details on oral exposure:

EXPERIMENTAL PREPARATION
- The test material was formulated within two hours of being applied to the test system and it was assumed that the substance was stable for that period of time.
- No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation and that decision was noted in the GLP compliance statement.

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Dosage volume: 10 mL/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

- Initial investigation: one female
- Second investigation: four females

Control animals:

no

Details on study design:

ANIMALS AND ANIMAL HUSBANDRY
- Animals were randomly allocated to cages on receipt.
- The females were nulliparous and non-pregnant.
- Animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card.
- Diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
- Animals were provided with environmental enrichment items that were considered not to contain any contaminant at a level that could affect the purpose or integrity of the study.

PROCEDURE
- Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
- In the absence of mortality at a dose level of 2000 mg/kg, an additional group of 4 animals was treated at a dose level of 2000 mg/kg.
- All animals were dosed once only by gavage.
- The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

OBSERVATIONS
- Clinical observations were made 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Morbidity and mortality checks were made twice daily.
- Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- At the end of the observation period all animals were subjected to gross necropsy consisting of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

- Motality data was used to obtain an estimate of the acute oral median lethal dose (LD50) of the test material.

Results and discussion

Preliminary study:

No mortality occurred at the preliminary dose level of 2000 mg/kg.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity of the test material was assessed according to OECD Guideline 420. The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute oral toxicity of the test item in the female Wistar rat, according to OECD Guideline 420, in compliance with GLP. Following an initial test in one animal at a dose level of 2000 mg/kg, a further group of four fasted animals was given a single oral dose of the test item at a dose level of 2000 mg/kg bw. There were no mortalities or signs of systemic toxicity during the study. All animals showed expected gains in bodyweight and no abnormalities were noted at necropsy. The acute oral LD50 of octadecanedioic acid, 1,18-dimethyl ester (ODDAME) in the female Wistar strain rat was therefore estimated to be greater than 2000 mg/kg bw (Harlan Laboratories Ltd, 2013).