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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 February 2012 to 28 February 2012
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:
2012

Materials and methods

Test guidelineopen allclose all
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)
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:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl dodec-9-enoate
EC Number:
700-618-7
Cas Number:
39202-17-0
Molecular formula:
C13H24O2
IUPAC Name:
Methyl dodec-9-enoate
Details on test material:
- Name of test material (as cited in study report): 9-dodecenoic acid, methyl ester (9DDAME)
- Physical state: clear colourless liquid
- Analytical purity: > 99 %
- Lot/batch No.: 184-109
- Date received: 2011-04-01
- Storage condition of test material: room temperature, under nitrogen, in the dark

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
- Weight at study initiation: 175 ± 20 %
- 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:
unchanged (no vehicle)
Details on oral exposure:
EXPERIMENTAL PREPARATION
- Specific gravity of the test material was determined and used to calculate the appropriate dose volume.
- 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
The test material was used as supplied.

MAXIMUM DOSE VOLUME APPLIED: 2.27 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 4 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:
- Data evaluations included the relationship, if any, between the animals' exposure to test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
- 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 toxicity was observed 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:
No signs of systemic toxicity were noted.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information 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.