Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, dioleates

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug 08, 1984 - Aug 22, 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reasonably wel reported and performed under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

yes

Remarks:

EPA GLP regulations of 29 Dec 1983

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(tallow alkyl )-1,3,propanediamine oleates

IUPAC Name:

N-(tallow alkyl )-1,3,propanediamine oleates

Test material form:

semi-solid (amorphous): gel

Remarks:

migrated information: paste

Details on test material:

Name: Duomeen TDO (AkzoNobel tradename for N-(tallow alkyl )-1,3,propanediamine oleates)
Batch: Lot #1400407
Common name:
Aspect: Tan Waxy Semi-Solid
pH: 4.5 @ 44°C
Specific Gravity: 0.87 @ 44°C

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: male and non-pregnant and nulliparous female Wistar Ablino rats, approximately 8 weeks old
- Weight at study initiation: between 200-300 grams,
- Fasting period before study: 16-20 hours prior to dosing.
- Housing: housed 5/sex/cage in suspended wire mesh cages. Bedding was placed beneath the cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not stated
- Humidity (%): not stated
(temperature and humidity controlled)
- Air changes (per hr): not indicated
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Aug 08, 1984 To: Aug 22, 1984

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

syringe and dosing needle at a dose level of 5.0 g/kg - no vehicle.
Sample preparation: 20 g of test article was heated gently to a melting point of 44°C

Doses:

Single dose 5.0 g/kg

No. of animals per sex per dose:

5 male + 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 2 and 4 hours post dose and once each morning and afternoon thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight. Abnormal tissues were preserved in 10% buffered formalin for possible future microscpic examination.

Statistics:

Not required for single dose: The LD 50 was considered to be greater than 5.0 g/kg if there was no compound related mortal ity at the 5.0 g/kg level.

Results and discussion

Preliminary study:

No

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 3/10 animals died at 5000 mg

Mortality:

3 females on observation days 7, 8 and 12 respectively.

Clinical signs:

other: Yes - see table under other information

Gross pathology:

Yes - see table under other information

Any other information on results incl. tables

Clinical signs (duration average number of days)

	Males	Females
		Death	Sarcrifice
Number treated	5	3	2
Diarrhea	1(1)	3(5)	2(4)
Piloerection	1(1)	3(3)
Ptosis	1(1)	2(2)
Emaciation	1(1)	1(1)
Lethargy		2(1)
Anogenital area stained brown	2(6)	3(7)	2(11)
Nose/mouth stained brown		3(6)	2(8)
Body surfaces soiled	1(2)

 

Necropsy observations

	Males	Females
		Death	Sarcrifice
Number necropsied	5	3	2
Normal			2
Cannibalized		2
Anogenital area stained brown		1
Lungs congested		1
Stomach areas red		1
Stomach distended with fluid		1	2(11)
Intestines red		1	2(8)
Intestines distended with fluid		1

 

Body weights:

Animal-sex	Dose vol. cc	Day 0 g	Day 7 g	Day 14 g
1-M	1.2	216	246	330
2-M	1.3	219	242	328
3-M	1.3	218	184	290
4-M	1.4	247	300	384
5-M	1.3	224	242	332
Mean		224.8	242.8	332.8
S.D.		12.8	41.1	33.5
6-F	1.2	209	188	234
7-F	1.5	253	270	322
8-F	1.3	218	202	dead d.12 (144 g)
9-F	1.3	218	164	dead d.8*
10-F	1.2	211	dead d.7*
Mean		221.8	206	278
S.D.		17.9	45.5	62.2

*Termina1 body weight was not recorded since the animals were cannibalized.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acute oral toxicity was determined in a limit test in 5 males and 5 females at 5 g/kg bw, undilted. LD50 > 5.0 g/kg bw for males and females combined.

Executive summary:

Method: Five healthy male and five healthy non-pregnant and nulliparous female albino rats were dosed orally with Duomeen TDO, Lot #1400407 at 5.0 g/kg of body weight.

The rats were observed 1, 2 and 4 hours post dose and twice daily for 14 days for mortality and toxicity. Body weights were recorded pretest, weekly, at death and at termination in the survivors. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.

Although there was compound related mortality, a multi-dose LD50 was not performed as per client request.

 

Results: Seven of ten animals survived the 5.0 g/kg oral dose.

Three females died between Day 7 and Day 12 with pre-death physical signs of diarrhea, lethargy, ptosis, piloerection, emaciation, soiling of body surfaces and brown staining of the nose/mouth and anogenital areas. Two animals which died were not necropsied since they had been cannibalized. The other death had abnormalities of the lungs and gastrointestinal tract, as well as brown staining of the anogenital area. Physical signs of chromorhinorrhea, diarrhea, piloerection, emaciation, ptosis, soiling of body surfaces, and brown staining of the nose/mouth and anogenital areas were noted in survivors and were more prevalent in females.

Body weight increases were normal in 5/7 survivors. One male and one female lost weight during the first week of the study.

Necropsy results were normal in survivors.

Conclusion: The LD 50 is greater than 5.0 g/kg in males, less than 5.0 g/kg in females and greater than 5.0 g/kg for combined sexes.