Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of N-[3-(Dimethylamino)propyl]stearamide and N-[3-(Dimethylamino)propyl]hexadecan-1-amide
Molecular formula:
Not relevant
IUPAC Name:
Reaction mass of N-[3-(Dimethylamino)propyl]stearamide and N-[3-(Dimethylamino)propyl]hexadecan-1-amide
Test material form:
solid
Details on test material:
Test material: DMAPSA (Octadecanamide, N-(3-(dimethylamino)propyl)-) (CAS No. 7651-02-7).
Date of receipt: 24th July 1990.
Description: White waxy solid.
Storage: In original container at room temperature.
Specific details on test material used for the study:
Description: white waxy soìid
Container: plastic screw-top container
Sponsor's identification: DMAPSA
Date of arrival: 24 July 1990
Storage conditions: room temperature




Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Bantin & Kingman Ltd., Grjmston, Aldborough, Hull, U.K.
- Age at study initiation: 5 to 8 weeks old
- Weight at study initiation: males: 124 - 157g; females 120 - 141g
- Housing: The animals were housed in groups of up to five by sex in solld-floor polypropyìene cages wjth sawdust beddìng.
- Diet and water (e.g. ad libitum): With the exception of an overnight fast immedjately before dosing and for approximateìy two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Wiitham,
Essex, U.K.) was allowed throughout the study.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-28
- Humidity (%): 46-67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
Range-finding study: All animals were dosed once onìy by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosìng.
Main study: All animals were dosed twice in a similar manner to that used in the range-finding study.
Doses:
Range-finding study: 200: 2000; 5000 mg/kg (corresponding to concentration of 500; 200 and 20 mg/ml, respectively, with dose volume of 10 ml/kg)
Main study: 5000 mg/kg (corresponding to concentration of 250 mg/ml, respectively, with dose volume of 2x10 ml/kg)*
*Due to the mortalities, an additional group of ten animals (five males and five females) were therefore treated as follows: 2000 mg/kg (corresponding to concentration of 200 mg/ml, respectively, with dose volume of 10 ml/kg)
No. of animals per sex per dose:
Range-finding study: 1
Main study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Deaths and overt signs of toxicity were recorded 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14, or at death.
- Necropsy of survivors performed: yes: At the end of the study the animals were killed by cervicaì dislocation and subjected to gross necropsy examination for any macroscopic abnormalities
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: This consisted of opening the abdominal and thoracic cavities and examining all major organs. The macroscopic appearance of abnormal organs if present was recorded. No tissues were retained.

Results and discussion

Preliminary study:
No mortality was observed in the range-finding study at 5000; 2000 and 200 mg/kg.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: range-finding study
Remarks:
(0/2 death at 5000mg/kg)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: main study
Remarks:
(7/10 deaths at 5000 mg/kg; 2/10 deaths at 2000 mg/kg)
Mortality:
None in range-finding study
Main study:
- at 5000 mg/kg:7 deaths/10 animals (3/5 for males and 4/5 females)
- at 2000 mg/kg: 2 deaths/10 animals (1/5 for males and 1/5 females)
Clinical signs:
Common or isolated incidents of toxicìty noted were hunched posture, pilo-erection, lethargy, ptosìs, ataxia, decreased respiratory rate, emaciation, djuresis, distended abdomen, red/brown stains around snout and dehydration.
Surviving animaìs appeared normal one to eleven days after dosing.
Body weight:
One male and one female treated with 5000 mg/kg showed bodyweight loss during the first week. All other surviving animals showed expected gain in bodyweight during the study.
Gross pathology:
One male treated with 2000 mg/kg that died during the study was found cannibalised. A necropsy was therefore not performed.
Abnormalities noted at necropsy of the female treated with 2000 mg/kg and animals treated with 5000 mg/kg that died during the study were haemorrhagic or abnormaìly red lungs, dark liver or patchy pallor of the liver, dark kidneys, haemorrhage of the gastric mucosa, haemorrhage of the non-glandular epithelium of the stomach and haemorrhage of the small and large intestines.
0ccasional white foci approximately 3 mm x 3 mm covering 25% of the non-glandular epithelium of the stomach was noted at necropsy of one female treated with 5000 mglkg that was killed at the end of the study.
No abnormalities were noted at necropsy of two males treated with 5000 mg/kg and anìmals treated with 2000 mg/kg that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute oral median lethal dose (LDSO) of the test material in the Sprague-Dawìey strain rat was found to be greater than 2000 mg/kg bw but less than 5000 mg/kg bw.
Executive summary:

A study has performed to assess the acute oral toxicity of the test material DMAPSA in the Sprague-Dawley strain rat. The method used followed that described in the OECD Gu'idelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity" referenced as Method B1 in Commission Directive 84/449/EEC.

The results may be used as a basis for classification and label'ling under Commission Directive 83/467/EEC and the U.K. Approved Code of Practice "Classification and Labelling of Substances Dangerous for Supply".

Following a range-finding study, two groups of ten fasted animals (five males and five femaìes) were gìven a single oral dose of test material preparation, administered as a suspension in arachis oil B.P. at dose

levels of 2000 and 5000 ng/kg bodyweight.

Deaths were noted one to five days after dosing. One male treated with 5000 mg/kg was killed in extremis six days after dosing. Common or isolated incidents of toxicity noted were hunched posture, pilo-erection, lethargy, ptosis, ataxia, decreased respiratory rate, emaciation, diuresis, distended abdomen, red/brown stains around snout and dehydration.

Surviving animaìs appeared normal one to eleven days after dosing.

One male and one female treated with 5000 mg/kg showed bodyweight loss during the first week. All other surviving animals showed expected gain in bodyweight during the study.

The male treated with 2000 mg/kg that died during the study was found canni balised. A necropsy was therefore not performed .

Abnormalities noted at necropsy of the female treated with 2000 mg/kg and animals treated with 5000 mg/kg that died during the study were haemorrhagic or abnormally red lungs, dark liver or patchy pallor the liver, dark kidneys, haemorrhage of the gastric mucosa, haemorrhage of the nonglandular epithelium of the stomach and haemorrhage of the smaìl and large intestines .

Occasional white foci approximately 3 mm x 3 mm covering 25% of the nonglandular epithelium of the stomach was noted at necropsy of one female treated with 5000 mg/kg that was killed at the end of the study.

No abnormalitjes h,ere noted at necropsy of two males treated with 5000 mg/kg and animals treated with 2000 mg/kg that were killed at the end of the study.

The acute oral median lethal dose (LD5O) of the test material in the Sprague-Dawìey strain rat was found to be greater than 2000 mg/kg bodyweight but less than 5000 mg/kg bodyweight. No symbol and risk phrase are required according to EEC labelling regulations.