Octadecanedioic acid, 1,18-dimethyl ester

Endpoint summary

Description of key information

Acute Oral Toxicity: 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.

Acute Dermal Toxicity (read-across from supporting substance, structural analogue EC 662-772-0): The acute dermal LD50 of the test item in the Wistar strain rat was found to be >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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

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.

Preliminary study:

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

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.

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study conducted to GLP and OECD guidelines.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

18 January 2012 to 01 February 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Read-across justification: A comparison target substance (9DDAME) and the read-across substance (9DAME) shows that the two substances share structural similarities, increasing from a chain length of C10 to C12 with similar functional groups and also have ‘mechanistic action’ similarities.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection 2011-07-19 to 2011-07-21; Date of signature 2011-08-31

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals/sex

Control animals:

no

Sex:

male/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: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 of 9-decenoic acid, methyl ester (9DAME) in the Wistar strain rat was found to be >2000 mg/kg bw.

Executive summary:

The acute toxicity of the test item 9-dodecenoic acid, methyl ester (9DDAME) via the dermal route has been read-across from the substance 9-decenoic acid, methyl ester from the following study:
A study was performed to assess the acute oral toxicity of the test item in the Wistar rat, according to OECD Guideline 402, in compliance with GLP. A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item it intact skin at a dose level of 2000 mg/kg bw. There were no mortalities or signs of systemic toxicity during the study. Very slight erythema was noted at the test sites of all males and one female. Small superficial scattered scabs were also noted at the test site of one male. There were no signs of dermal irritation noted in four females. Animals showed expected gains in bodyweight over the study period except for one female which had a slight bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy. The acute dermal LD50 of 9-decenoic acid, methyl ester in the Wistar strain rat was therefore estimated to be greater than 2000 mg/kg bw (Harlan Laboratories Ltd, 2012). Based on the results of the read across study, a similar result can be expected for the test item.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study conducted to GLP and OECD guidelines.

Additional information

Acute oral toxicity:

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).

 

Acute dermal toxicity:

The acute toxicity of the test item 9-dodecenoic acid, methyl ester (9DDAME) via the dermal route has been read-across from the substance 9-decenoic acid, methyl ester from the following study:
A study was performed to assess the acute oral toxicity of the test item in the Wistar rat, according to OECD Guideline 402, in compliance with GLP. A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item it intact skin at a dose level of 2000 mg/kg bw. There were no mortalities or signs of systemic toxicity during the study. Very slight erythema was noted at the test sites of all males and one female. Small superficial scattered scabs were also noted at the test site of one male. There were no signs of dermal irritation noted in four females. Animals showed expected gains in bodyweight over the study period except for one female which had a slight bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy. The acute dermal LD50 of 9-decenoic acid, methyl ester in the Wistar strain rat was therefore estimated to be greater than 2000 mg/kg bw (Harlan Laboratories Ltd, 2012). Based on the results of the read across study, a similar result can be expected for the test item.

Justification for classification or non-classification

 

The acute oral LD50 in rats for octadecanedioic acid, 1,18-dimethyl ester (ODDAME) was > 2000 mg/kg bw. Therefore, this substance does not require classification for acute oral toxicity according to the criteria described in Regulation (EC) No 1272/2008.

The acute dermal LD50 in rats for a structural analogue substance was >2000 mg/kg bw. Therefore, the substance does not require classification for acute dermal toxicity according to the criteria described in Regulation (EC) No 1272/2008.