Registration Dossier

Administrative data

Description of key information

RA-S CAS 16260-09-6 and CAS 13276-08-9, OECD 401, rat: LD50 > 2400 mg/kg bw
RA-S CAS 16260-09-6, OECD 402, rat: LD50 > 2000 mg/kg bw
Inhalation: no study available

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 400 mg/kg bw
Quality of whole database:
GLP guideline studies with structurally related substances according to the criteria of Regulation (EC) No 1907/2006. Annex XI, paragraph 1.5. Reliability of study originally Klimisch 1, but reliability was changed to "2" according to the ECHA guidance document "Practical guide 6: How to report read-across and categories".

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Reliability was changed from "1" to "2" according to the ECHA guidance document "Practical guide 6: How to report read-across and categories".
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
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 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-hour 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.

CONCLUSION:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP guideline study with a structurally related substance according to the criteria of Regulation (EC) No 1907/2006. Annex XI, paragraph 1.5. Reliability of study originally Klimisch 1, but reliability was changed to "2" according to the ECHA guidance document "Practical guide 6: How to report read-across and categories".

Additional information

There is no data available on the acute toxicity of (Z)-N-octadecyldocos-13-enamide (CAS 10094-45-8). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, and in accordance with Annex XI, 1.5 of Regulation (EC) No 1907/2006, read-across from structurally related substances is conducted.

A detailed justification for the analogue approach is provided in the technical dossier (see IUCLID sections 7.1 and 13).

 

Oral

There are two studies available for the acute oral toxicity of the structurally related substances (Z)-N-octadec-9-enylhexadecan-1-amide (CAS 16260-09-6) and N-octadecylstearamide (CAS 13276-08-9), which were used for read-across based on an analogue approach.

The acute oral toxicity of (Z)-N-octadec-9-enylhexadecan-1-amide (CAS 16260-09-6) was investigated in a GLP-conform study performed according to OECD 401 (Thouin, 1986). The test substance diluted in corn oil was administered to 5 Wistar rats per sex at a limit dose of 2400 mg/kg bw by oral gavage. During the 14-day observation period, no mortality and no clinical signs were observed, except for lethargy which was frequently observed among the animals on Day 1 after treatment. The weekly body weight gain of the animal was normal during the study, and no substance-related gross abnormalities were noted at necropsy. Based on these observations, the oral LD50 value in male and female rats was > 2400 mg/kg bw.

In an acute oral toxicity study with N-octadecylstearamide (CAS 13276-08-9) according to OECD 401 performed under identical conditions as described above, oral gavage of the test substance in corn oil to 5 male and 5 female Wistar rats at a limit dose of 2400 mg/kg bw did not result in any mortalities, clinical signs of toxicity, changes in body weights and gross pathological findings during the 14-day observation period (Thouin, 1986). Therefore, the oral LD50 value in male and female rats was > 2400 mg/kg bw.

 

Inhalation

In accordance with Regulation (EC) 1907/2006, Annex VIII, Section 8.5.2, column 2, testing by the inhalation route is appropriate if exposure of humans via inhalation is 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. The substance (Z)-N-octadecyldocos-13-enamide is a solid with very low vapour pressure (4.9E-05 Pa at 20 °C) and does not contain respirable particles in a significant amount. Thus, exposure of humans via inhalation is unlikely. Therefore, testing for acute toxicity by the inhalation route is not appropriate and should be avoided for reasons of animal welfare. In addition, reliable data for acute toxicity via the oral and dermal route is available for structurally related substances according to Regulation (EC) No 1907/2006, Annex XI, article 1.5.

 

Dermal

A reliable study on the acute dermal toxicity of the structurally related substance (Z)-N-octadec-9-enylhexadecan-1-amide (CAS 16260-09-6) is available, which is used for read-across based on the analogue approach.

An acute dermal toxicity study with (Z)-N-octadec-9-enylhexadecan-1-amide (CAS 16260-09-6) was performed according to OECD 402 and under conditions of GLP (Bradshaw, 2012). Five RccHan:WIST rats per sex were exposed to the test substance diluted in arachis oil at a limit dose of 2000 mg/kg bw for 24 h under semiocclusive dressing. During the 14-day observation period, no mortality and clinical signs of toxicity were observed, and no gross pathological changes were noted at necropsy. All animals showed the expected body weights during the study, except for one male which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. 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. Based on the results of this study, a dermal LD50 value > 2000 mg/kg bw was derived for male and female rats.

Based on the available data on acute oral and dermal toxicity of the structural analogues, it may be concluded that (Z)-N-octadecyldocos-13-enamide (CAS 10094-45-8) does not exert acute toxicity via the oral and dermal route, either.


Justification for selection of acute toxicity – oral endpoint
There are two studies available for the acute oral toxicity of two structurally related substances. No study was selected, since both studies are considered to be equivalent key studies regarding to their reliability, quality of dose descriptor and time of study implementation.

Justification for selection of acute toxicity – dermal endpoint
There is only one study for acute dermal toxicity of a structural related substance available.

Justification for classification or non-classification

The available data on the acute toxicity of (Z)-N-octadec-9-enylhexadecan-1-amide (CAS 16260-09-6) and N-octadecylstearamide (CAS 13276-08-9), which are structurally related substances to (Z)-N-octadecyldocos-13-enamide (CAS 10094-45-8) according to the criteria of Regulation (EC) No 1907/2006, Annex XI, 1.5, do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC; therefore, (Z)-N-octadecyldocos-13-enamide (CAS 10094-45-8) is not expected to exert acute toxicity, either, and the data are conclusive but not sufficient for classification.