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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-05-16 to 1988-06-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February, 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
84/449/EEC
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Fettsauredimethylaminopropylamid
IUPAC Name:
Fettsauredimethylaminopropylamid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Firma Charles River Wiga, Sandhofer Weg 7, 8741 Sulzfeld
- Age at study initiation: no data
- Weight at study initiation: males: 208 - 250 g, females: 160 - 190 g
- Fasting period before study: 16 h before until 4 h after administration of the test article
- Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type III)
- Diet: ad libidum, standard laboratory rat diet Ssniff-R
- Water: ad libitum, aqua fontana as for human consumption
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/-2 °C
- Humidity: 50-80 %
- Air changes (per hr): no data
- Photoperiod: fluorescent light (120 lux), 12 hours daily from 7.00 a.m. - 7.00 p.m.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Doses:
2500, 3000, 4000, and 5000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Preparation of the test compound: For treatment the sample was liquified at a temperature of about 45 °C and then diluted with warm Oleum arachidis by using a magnetic stirrer. For dosing the dilution was cooled down to about 35 °C. The following concentrations were used: .25 %, 30 % and 50 %. The pH-value was 6.6.
- Duration of observation period following administration: 14 days
- Frequency of weighing: The body weights were recorded at day 0 (beginning of the experiment), at day 7 and at day 14 (terminal necropsy) on the surviving animals.
- Clinical observations: The evaluation of the clinical-toxicological signs (a modified Irvin-Screening by Screening methods in pharmacology, R. A. Turner, 1965) was done individually and depends on the nature of the signs. If the symptoms persist to the same degree for a longer period of time, this was noted in the corresponding protocols. Only a change of symptoms was recorded. Records were made according to the following intervals: about 20', 1 + 2 h, 3 + 6 h, 24 h, thereafter once daily up to day 14.

- Necropsy of survivors performed: yes. Additionally, immediately after death a complete necropsy was performed on all acute- and late mortalities.
Statistics:
If possible, the calculation of the LD50 was done according to Finney D.Y.: Probit Analysis, 3. edition, Cambridge 1971.

Results and discussion

Preliminary study:
Four female rats were employed in a preliminary range finding study. The dosage of the single oral administration were 5000 and 2500 mg/kg of body weight.
At the dosage of 5000 mg/kg both treated animals died within 48 h p.a.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 647
95% CL:
3 114 - 4 567
Sex:
female
Dose descriptor:
LD50
Effect level:
3 317
95% CL:
2 596 - 3 853
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 478
95% CL:
3 108 - 3 878
Mortality:
2500 mg/kg bw: 0/5 males and 0/5 females
3000 mg/kg bw: 1/5 males and 2/5 females
4000 mg/kg bw: 3/5 males and 4/5 females
5000 mg/kg bw: 5/5 males and 5/5 females
Clinical signs:
other: The sample induced in the tested dosages in a high degree mainly obviously reduced activity partly with apathy, obvious disturbance of coordination, reduced reflex excitability, cyanosis/paleness of the mucous membrane, slight to obvious piloerection, mai
Gross pathology:
The mortalities showed at autopsy partly slight redness of the mucous membrane of the digestive system and solid residues of the sample.
Nothing abnormal was found in all animals necropsied at termination.

Any other information on results incl. tables

Number of animals dead and time range within which mortality occurred

 

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths

Male

Female

Combined

2500

0/5

 0/5

 0/10-

 -

3000

 1/5

2/5 

 3/10

 3 to 6/14 days

4000

 3/5

4/5 

 7/10

 3 to 6/14 days

5000

 5/5

5/5 

 10/10

 1 to 6/14 days

 

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
On the basis of the results obtained after a single oral administration, the oral LD50 after 14 d of the test article (in arachis oil) was determined to be 3478 mg/kg bw . No significant effects on body weight were observed. The sample induced reduced activity (apathy), disturbance of coordination, reduced reflex excitability, cyanosis/paleness, piloerection, reduced body temperature and kachexia.
The mortalities showed residues of the sample in the digestive system and redness of the mucous membrane of the digestive system. Nothing abnormal was found in the animals necropsied on day 14.
Therefore the test substance was judged to be practically non- toxic based on the LD50 in males and females.
Executive summary:

In an acute oral toxicity study (standard acute method, according to OECD 401 (February, 1987) and the EEC directive 84/449 EEC), groups of 5 male and 5 female Wistar rats were given single oral doses of the substance in arachis oil and observed for 14 days.

Oral LD50 Males and Females combined after 14 days 3478 (3108 - 3878) mg/kg of body weight

Oral LD50 Males after 14 days: 3647 (3114 - 4567) mg/kg of body weight

Oral LD50 Females after 14 days: 3317 (2596 - 3853) mg/kg of body weight

The sample induced reduced activity (apathy), disturbance of coordination, reduced reflex excitability, cyanosis/paleness, piloerection, reduced body temperature and kachexia.

Post-dosing weight gains (2 week values) of the surviving animals did not show essential differences.

The mortalities showed residues of the sample in the digestive system and redness of the mucous membrane of the digestive system.

Nothing abnormal was found in the animals necropsied on day 14.

The test subance was judged to be practically non-toxic based on the oral LD50 in male and female rats.

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