9-Octadecenamide, N-[(1S,2S,3R)-2,3-dihydroxy-1-(hydroxymethyl)heptadecyl]-, (9Z)-

Endpoint summary

Description of key information

Acute toxicity: oral

- Key study, read-across, source substance Ceramide III, OECD guideline 401 and EU Method B.1, GLP, Reliability 1: Oral LD₅₀ (rat) > 5000 mg/kg bodyweight

- Supporting study, target substance Ceramide IIIB, similar to OECD guideline 401, Reliability 2: Oral LD₅₀ (rat) > 2000 mg/kg bodyweight

Acute toxicity: dermal

- Key study, target substance Ceramide IIIB, similar to OECD guideline 402, Reliability 2: Dermal LD₅₀ (rat) > 2000 mg/kg bodyweight

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-02-05 to 1992-02-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted February 24, 1987.

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

September 1984

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

The formulations were prepared immediately prior to dosing. The test substance was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added. Adjustment was made for specific gravity of vehicle. Homogeneity of the test substance in vehicle was obtained using a homogeniser and a spatula.

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: Male= 198 to 209 g, female= 150 to 164 g
- Fasting period before study: yes, feed was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Collection caging in polycarbonate cages / max. 5 rats
- Diet (e.g. ad libitum): laboratory animal diet (KLIB 343 from Klingentalmühle AG, Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 55 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours daily

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

Dose volume: 10 mL/kg bw
DOSAGE PREPARATION: 5000 mg/kg bw were achieved by administration of two times 2500 mg/kg bw

Doses:

5000 mg/kg bw, given as 2 dosages of 2500 mg/kg bw within 24 hours. Multiple dosages given within 24 hours are regarded as a single dose.

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
mortality: twice daily
clinical signs: 0, 2, 4 h, daily thereafter
- Frequency of weighing: Days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes

Preliminary study:

-Pilot study with three groups, each comprising of 1 male and 1 female rat
-orally dosed with test material in propylene glycol at 5000 (2x2500 within 24 hours), 2000 or 1000 mg/kg body weight
- no animal died.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality occurred.

Clinical signs:

other: Signs of ill health or behavioural changes included ataxia only observed in all animals approximately 2 hours after each dosing.

Gross pathology:

Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were not commonly noted among rats of this age and strain or that were considered toxicologically significant. Pelvic dilation (left and right kidney) in a single female rat was considered not to be related to the treatment.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

In this acute oral toxicity study, the oral LD50 value of the test item in rats of either sex was exceeding 5000 mg/kg bodyweight.

Executive summary:

In an acute oral toxicity study according to OECD guideline 401 (adopted February 24, 1987) and EU Method B.1 (September 1984), 5 male and 5 female, fasted, 8-9 weeks old Wistar strain rats were given a single oral dose of Ceramide III in propylene glycol by gavage at a dose of 5000 mg/kg bw and daily observed for 14 days. Body weight was determined at day 1 (pre-administration), 8 and 15.

Ceramide III was administered as 2 dosages of 2500 mg/kg bw within 24 hours. Multiple dosages given within 24 hours are regarded as a single dose.

No animal died. Apart from ataxia noted after each dosing, no other signs of ill health or behavioural changes were observed during the study period and no macroscopic toxicologically significant abnormalities were noted at necropsy at the end of the experimental period.

Oral LD₅₀ (rat) > 5000 mg/kg bodyweight

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Between 1995-01-03 and 1995-01-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

only basic data given; experimental period 8 days; only 4 animals tested

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

only 4 animals tested, experimental period only 8 days

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

no information available

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

Dose volume: 10 mL/kg bw

Doses:

2000 mg/kg body weight (dose volume 10 ml/kg body weight)

No. of animals per sex per dose:

2 males, 2 females

Control animals:

no

Details on study design:

Animals were subjected to daily observations and determination of body weight at start and termination. Macroscopic examination of the animals was performee at the end of the experimental period (day 8).

Preliminary study:

Not reported.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality occurred.

Clinical signs:

other: All animals showed slightly uncoordinated movements two and four hours after treatment. Piloerection was observed in a single female animal two hours after treatment.

Gross pathology:

Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were not commonly noted among rats of this age and strain or that were considered toxicologically significant.

Other findings:

none reported.

Interpretation of results:

GHS criteria not met

Conclusions:

In this acute oral toxicity study, the oral LD50 value of the test item in rats of either sex was exceeding 2000 mg/kg bodyweight.

Executive summary:

In an acute oral toxicity study similar to OECD guideline 401, 2 male and 2 female Wistar strain rats were given a single oral dose of Ceramide IIIB in propylene glycol by gavage at a dose of 2000 mg/kg bodyweight. The animals were observed daily for a period of 8 days. Body weight gain was determined.

No animal died. Apart from uncoordinated movements and piloerection after dosing, no other signs of ill health or behavioural changes were observed during the study period and no macroscopic toxicological significant abnormalities were noted at necropsy at the end of the experimental period.

Oral LD₅₀ (rat) > 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:

Two reliable study reports on acute oral toxicity prove that the given data are of high quality.

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:

experimental study

Adequacy of study:

key study

Study period:

Between 1995-01-03 and 1995-01-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

only basic data given; experimental period only 8 days; only 4 animals tested

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

experimental period 8 days only, only 4 animals tested

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

no information available

Type of coverage:

not specified

Vehicle:

propylene glycol

Details on dermal exposure:

no information given

Duration of exposure:

no information given

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

2 males and 2 females

Control animals:

not specified

Details on study design:

One group of Wistar rats, consisting of two males and two females, received a single dermal application of the test substance suspended in propylene glycol at a dose level of 2000 mg/kg body weight (dose volume 10 mL/kg body weight).
Animals were subjected to daily observations and determination of body weight at start and termination.
Macroscopic examination of the animals was performed at the end of the experimental period (day 8).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

No abnormalities were found at macroscopic examination of the animals.

Other findings:

None described.

Interpretation of results:

GHS criteria not met

Conclusions:

According to this study, the dermal LD50 value of the test substance for both males and females was considered to exceed 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study similar to OECD guideline 402, 2 male and 2 female Wistar strain rats were given a single dose of Ceramide IIIB suspended in propylene glycol at a dose level of 2000 mg/kg body weight (dose volume 10 mL/kg body weight). Animals were subjected to daily observations and determination of body weight at start and termination. Macroscopic examination of the animals was performed at the end of the experimental period (day 8).

No animal died. No effect on body weight gain was observed. No clinical signs were observed during the study period and no macroscopic toxicological significant abnormalities were noted at necropsy at the end of the experimental period.

Dermal LD₅₀ (rat) > 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:

The given report contains basic information, but the outcome of the acute dermal toxicity study is strongly supported by the results from acute oral toxicity studies.