[R-(Z)]-N-[3-(dimethylamino)propyl]-12-hydroxy-9-octadecenamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-05-31 to 2012-06-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The justification for use of alternative data for the acute oral toxicity is provided in section 13 of this substance dossier.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Specific details on test material used for the study:

PC-2012-417

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-9 weeks
- Fasting period before study: overnight prior to dosing and until approximately 1 hour after the second administration of the test substance
- Housing: 3/cage
- Diet (e.g. ad libitum): pelleted rodent diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24°C
- Humidity (%): 40-70%
- Air changes (per hr): app. 15/h
- Photoperiod (hrs dark / hrs light):12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10% w/w
- Amount of vehicle (if gavage): 10 mL/kg bw

DOSAGE PREPARATION (if unusual):
2000 mg/kg bw were achieved by administration of two times 1000 mg/kg bw, since a 20% w/w formulation was not homogenous based on trial formulations.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 female rats per treatment group

Control animals:

no

Statistics:

not applicable

Results and discussion

Preliminary study:

The vehicle was selected based on trial formulations performed at WIL and on the test substance data supplied by the Sponsor (stability for at least 5 hours at room temperature is confirmed over the concentration range 4 to 40 mg/mL, project 501394.
The total dose was administered as two dosages of 1000 mg/kg bw each (the first on t=0 and the second on t=5 hours), since a 20%w/w formulation was not homogenous based on trial formulations.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: According to OECD 423 (2001), the LD50 cut-off value was considered to be 2500 mg/kg bw.

Mortality:

One female of the first group and one female of the second group at 2000 mg/kg bw were found dead on Days 2 and 3, respectively.

Clinical signs:

Clinical signs shown by the animals found dead and surviving animals included lethargy, hunched posture, uncoordinate movements, piloerrection, diarrhoea, chromodacryorrhoea, pallor, and/or ptosis. The suviving animals had recovered from the symptoms between Days 7 and 10.

Body weight:

The two animals found dead showed either slight weight gain or weight loss. Three out of four surviving females showed body weight loss between Days 1 and 8. These animals agoin gained body weight between Days 8 and 15.One surviving female showed body weight gain that was considered to be similar to that of normal untreated animals of the same age and strain.

Gross pathology:

One female found dead showed watery-clear fluid in the stomach and watery-clear, yellowish fluid in the small intestine. The other female found dead showed a reduced size of the spleen. Pelvic dilation of the kindneys was noted in one surviving female. Other surviving females had no macroscopic abnomalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Data conlusive but no sufficient for classification based on CLP criteria (Regulation (EC) No 1272/2008).

Conclusions:

According to the OECD 423 test guideline, the oral LD50 of Stearic acid 3-(dimethylaminopropyl)amide in female rats was > 2000 mg/kg bw.