Registration Dossier

Administrative data

Description of key information

Oral Route:

In an OECD 420 study, conducted according to GLP, the LD50 of the test material in female rat was estimated to be greater than 2,000 mg/kg bodyweight.

Inhalation route:
The study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. This endpoint is waived.
Dermal route:

In an OECD 402 test guideline study, conducted according to GLP, the acute dermal toxicity (LD50) of the structually similar read across substance to rats is greater than 2,000 mg/kg bodyweight.


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:
April 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
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no
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: eight to twelve weeks
- Weight at study initiation: 164 g. Body weight variation did not exceed +/- 20% of the body weight of the initially dosed animals.
- Fasting period before study: Overnight fast immediately before dosing and approximately three to four hours after dosing.
- Housing: suspended solid floor polypropylene cages furnished with wood chippings.
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): Fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light and twelve hours darkness.
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Arachis oil was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED:
2,000 mg/kg
Doses:
In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
In the absence of toxicity at the dose level of 300 mg/kg, an additional dose level of 2,000 mg/kg was included.
No. of animals per sex per dose:
300 mg/kg - 1 animal
2,000 mg/kg - 5 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 1/2, 1, 2 and 4 hours after dosing, and then daily for fourteen days. Individual body weights were recorded on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: external examination, opening abominal and thoracic cavities.
Preliminary study:
There was no mortality; no signs of systemic toxicity were noted during the observation period.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All animals showed expected gains in body weight 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 LD50 of the test material in female Wistar strain rat was estimated to be greater than 2,000 mg/kg bodyweight.
Executive summary:

In an OECD 420 test guideline, conducted according to GLP conditions, the acute oral toxicity (LD50) of the test material to female Wistar rats is greater than 2,000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
1

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:
supporting study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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:
Department of Health, UK
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: RccHan:WIST
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, weight variation did not exceed ±20% of the mean for each sex
- Fasting period before study: not required
- Housing: housed individually during the 24-h exposure period and in groups of five, by sex, for the remainder of the study in suspended solid-floor polypropylene cages furnished with woodflakes. Animals were provided with environmental enrichment items considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet: 2014C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped back and flanks
- % 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): treated skin and surrounding hair were wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable, only used for moistening of the test substance
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
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. Individual body weights were recorded prior to application on Day 0 and on Days 7 and 14
- Necropsy of survivors performed: yes, all animals
- Other examinations performed: clinical signs, body weight, external examination, opening of the abdominal and thoracic cavities, appearance of macroscopic abnormalities. After removal of the dressings and subsequently once daily for fourteen days the test sites were examined for primary irritation and scored according to the criteria of Draize (1977).
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No signs of systemic toxicity were observed.
Body weight:
Animals showed expected gains in bodyweight over the study period except for one male which showed 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:
- Other observations: Dermal reactions: very slight erythema was noted at the test sites of 4/5 females (score 1) which abated after 5 days in 3 females and after 8 days in the fourth. There were no signs of dermal irritation noted at the test sites of the remaining animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of N-octadec-9-en-1-ylhexadecanamide in the Wistar strain rat was found to be greater than 2000 mg/kg bw.
Executive summary:

In an OECD 402 test guideline study, conducted according to GLP, the acute dermal toxicity (LD50) of the structually similar read across substance to rats is greater than 2,000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
1

Additional information

The registration of the test material employs a combined approach for addressing the required endpoints. When data are not available, data from the read across substances are used to address the required endpoints.

 

The read across substances are structurally similar to registered substance. The substance and the proposed structural analogues are predominantly C32 – C36 alkyl fatty amides. These substances are expected to be metabolised by fatty acid amide hydrolase and esterases. Any differences among the substance structures are not expected to result in any significant differences in the toxicological effects or degradation products.

 

The following endpoints include supporting studies to provide evidence of read across suitability:

 

  • Acute toxicity, dermal route

Oral route:

In an OECD 420 test guideline, conducted according to GLP conditions, the acute oral toxicity (LD50) of the test material to female Wistar rats is greater than 2,000 mg/kg bodyweight.

 

Inhalation route:

The study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. This endpoint is waived.

 

Dermal route:

In an OECD 402 test guideline study, conducted according to GLP, the acute dermal toxicity (LD50) of the structually similar read across substance to rats is greater than 2,000 mg/kg bodyweight.


Justification for selection of acute toxicity – oral endpoint
Study completed according to OECD Guideline under GLP conditions.

Justification for selection of acute toxicity – inhalation endpoint
According to 8.5.2 Column 2 Annex VIII of Regulation (EC) 1907/2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), the acute toxicity ,via inhalation route, of a substance does not need to be conducted if exposure of humans via inhalation is unlikely, taking into account the vapour pressure (for liquids) and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. The test material is a waxy solid block, where a particle size study could not be completed due to the waxy nature of the substance at room temperature thus human exposure is considered unlikely, therefore, this endpoint is waived.

Justification for selection of acute toxicity – dermal endpoint
Read across study completed according to OECD Guideline under GLP conditions.

Justification for classification or non-classification

Oral route:

The acute oral toxicity (LD50) of the test material to female Wistar rats is greater than 2,000 mg/kg bodyweight.

According to Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP), a substance is considered classified for acute toxicity (oral route) if the LD50 is less than 2,000 mg/kg bodyweight.

The test material is, therefore, considered not classified for acute toxicity via the oral route.

 

Dermal route:

Based on data from the read across substance the acute dermal toxicity (LD50) of the test material is expected to be greater than 2,000 mg/kg bodyweight (rats).

According to Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP), a substance is considered classified for acute toxicity (dermal route) if the LD50 is less than 2,000 mg/kg bodyweight.

The test material is, therefore, considered not classified for acute toxicity via the dermal route.