Registration Dossier

Diss Factsheets

Administrative data

Description of key information

• Oral LD50 > 2000 mg/kg bodyweight (OECD 420)
• Dermal LD50 > 2000 mg/kg bodyweight (OECD 402, read-across)

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:
02 February 2012 to 28 February 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP 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)
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
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
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.
Preliminary study:
No toxicity was observed 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:
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.
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
migrated 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:
other: see 'Remark'
Remarks:
Read-across from a GLP guideline study. 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.
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
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: at least 200 g
- Fasting period before study: No data
- Housing: Animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 hour exposure period and in groups of 5, by sex, for the remainder of the study.
- Diet: available ad libitum
- Water: mains drinking water available ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70%
- Air changes: at least 15 changes per hour
- Photoperiod: 12 hours light (06:00 to 18:00) and 12 hours darkness
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: On the day before treatment the back and flanks of each animal were clipped free of hair.
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin and the surrounding hair was wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2.26 mL/kg
- The test material was used as supplied.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Necropsy of survivors performed: All animals were subjected to gross necropsy. The appearance of any macroscopic abnormalities were recorded. No tissues were retained.
- Other examinations performed: clinical signs, body weight: Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
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:
There were no signs of systemic toxicity.
Body weight:
Animals showed expected gains in bodyweight over the study period except for one female which showed a slight bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
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.

Individual dermal reactions- male

Dose Level

mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Male

Erythema

0

1

1

1

1

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1

Male

Erythema

0

0

1

1

1

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2

Male

Erythema

0

1

1

1

1

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3

Male

Erythema

0

0

1

1

1

1

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-4

Male

Erythema

0

0

1

1

1

1

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

Ss

Ss

Ss

0

0

0

0

0

0

0

0

0

0= no reactions

Ss= small superficial scattered scabs

Individual dermal reactions- female

Dose Level

mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0

female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

female

Erythema

0

1

1

1

1

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3

female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-4

female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0= no reactions

 

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity

A reliable study was performed in accordance with GLP and OECD Guideline 420 to assess the acute oral toxicity of 9-dodecenoic acid, methyl ester (9DDAME) in the female Wistar strain rat (Harlan Laboratories Ltd, 2012). Following an initial test in one animal at dose levels 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 9-dodecenoic acid, methyl ester

in the female Wistar strain rat was therefore estimated to be greater than 2000 mg/kg bw.

Acute inhalation toxicity

9-Dodecenoic acid, methyl ester has been shown by experiment to have a low vapour pressure (0.99 Pa) and the chemical safety assessment shows that exposure to aerosols or droplets of inhalable size is unlikely under normal conditions. In addition, there were no signs of systemic toxicity in the acute oral toxicity study performed with 9-Dodecenoic acid, methyl ester nor the dermal toxicity study performed with 9-decenoic acid, methyl ester, used in a read-across approach. Further investigations involving vertebrate animals are therefore contraindicated on the grounds of rodent welfare and hence an acute inhalation study is considered scientifically unjustified.

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 reliable study was performed in accordance with GLP and OECD Guideline 402 to assess the acute dermal toxicity of 9-decenoic acid, methyl ester in the Wistar strain rat (Harlan Laboratories Ltd, 2012). 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.

Justification of read-across: A comparison of 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.


Justification for selection of acute toxicity – oral endpoint
The study has been conducted according to OECD Guideline 420 and to GLP and is adequately reported. As such the study as been assigned a reliability 1.

Justification for selection of acute toxicity – dermal endpoint
The acute toxicity of the test item 9-dodecenoic acid, methyl ester (9DDAME) via the dermal route has been read-across from a study conducted with the substance 9-decenoic acid, methyl ester (9DAME). The study was conducted according to OECD Guideline 402 and to GLP and is adequately reported. As such the study as been assigned a reliability 1.

Justification for classification or non-classification

The acute oral LD50 in rats for 9 -dodecenoic acid, methyl ester was > 2000 mg/kg bw. The dermal LD50 value in rats for 9-decenoic acid, methyl ester was > 2000 mg/kg bw, which has been used in a read-across approach. No inhalation data is available but the substance has low vapour pressure and no effects were seen in oral and dermal studies. Therefore, 9-dodecenoic acid, methyl ester does not require classification for acute oral, dermal or inhalation toxicity according to the criteria described in Regulation (EC) No 1272/2008.