Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 January 1987 - 28 January 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A study was performed under GLP and generally according to OECD 401, but not using 5 animals of one sex per group. Limited data on test substance identity; no data on batch number, no Certificate of Analysis.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Instead of "At least 5 rodents are used at each dose level. They should all be of the same sex", in this study 4 rats are used per dose level, 2 male and 2 female animals.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Amines, N-(3-aminopropyl)-N’-[3-(C18 and C18-unsatd. alkyl amino)propyl]trimethylenedi and amines, N-(3-aminopropyl)-N’-(C18 and C18-unsatd. alkyl)trimethylenedi-
EC Number:
628-862-9
Cas Number:
1219458-11-3
Molecular formula:
UVCB - No molecular formula; Avg mw = 390.26 mw C16 Tetramine = 412.751 mw C18 Tetramine = 440.805
IUPAC Name:
Amines, N-(3-aminopropyl)-N’-[3-(C18 and C18-unsatd. alkyl amino)propyl]trimethylenedi and amines, N-(3-aminopropyl)-N’-(C18 and C18-unsatd. alkyl)trimethylenedi-
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): Tallow tripropylenetetramine
- Substance type: White paste
- Physical state: solid
- Analytical purity: (Certificate of Analysis is included in report)
- Impurities (identity and concentrations): Free Acrylonitrile < 4ppm and water 0,2%
- Composition of test material: see Certificate of Analysis.
- Purity test date: 05 February 2009
- Lot/batch No.: S001255
- Expiration date of the lot/batch: 23 January 2018
- Stability under test conditions: Yes: analytical verification of doses or concentrations performed
- Storage condition of test material: At room temperature in the dark under nitrogen.
- Other:
Density: 850 kg/m3 at 60°C
pH (1% in water, indicative range): 11.0
Stability at higher temperatures: Yes, maximum temperature: 80°C
Maximum duration: several hours
Solubility in Propylene glycol: Unknown

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, FRG
- Age at study initiation: 7 weeks
- Weight at study initiation: males on day 0 ranged from 271 to 306 g, females from 174 to 210 g
- Fasting period before study: overnight
- Housing: individually housed i n polycarbonate cages
- Diet (e.g. ad libitum): ad libitum,standard laboratory animal diet (RMH-B, pellet diameter 10 mm), obtained from Hope Farms, Woerden, The Netherlands.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 45-75
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 January 1987 To: 28 January 1987

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): 10ml/kg
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10ml/kg

DOSAGE PREPARATION (if unusual):
On the day of dosing the test substance was suspended in propylene glycol and heated to 35ºC in order to get a homogeneous suspension and administered as a single dose using a stainless steel stomach cannula.

Doses:
25, 200, 2000 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cage-side observations were performed on the day of dosing (once every two hours) and daily thereafter. Individual body weights (with group means) were measured weekly. Body weights were also measured at death when found dead 24 hours or more following dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
none

Results and discussion

Preliminary study:
not performed
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Mortality:
At 2000 mg/kg bw all animals died. One on the day of dosing and the others on day 1. At the other dose levels no deaths occurred.
Clinical signs:
Signs of toxicity, lethargy and a rough fur, were only observed in animals of the high dose group. At the other dose levels no signs of toxicity were observed.
Body weight:
No effects observed.
Gross pathology:
Macroscopic examination o f animals at necropsy showed no abnormalities in the low and mid dose group and petechiae; a yellow liquid intestinal content and gas accumulation in the intestines in all animals of the high dose group.
Other findings:
none

Applicant's summary and conclusion

Conclusions:
The oral LD50 value of Tallow tripropylene tetramine in Wistar rats is within the range of 300-2000 mg/kg body weight.
LD50 cut-off value is 500 mg/kg body weight.
Executive summary:

Three groups of Wistar rats; each comprising 2 males and 2 females, received a single oral dose at 25, 200 and 2000 mg/kg body weight; respectively. The incidence of mortalities for the sexes combined from low to high dose group was 0, 0 and 4. There was no evident sex related effect. All deaths occurred within 1 day of dosing. Signs of toxicity in animals of the high dose group were lethargy and a rough fur. No abnormal clinical behaviour was observed in animals of the 25 mg/kg and 200 mg/kg dose groups and no abnormalities at necroscopy. Group mean body weight gain for animals of the low and mid dose groups was nomal. Macroscopic examination of animals at necropsy revealed in all animals of the high dose group petechiae of the stomach, a yellow liquid intestinal content and gas accumulation in the intestines.

Based on the absence of signs of toxicity in the 200 mg/kg group as well as the absence of abnormalities in this group at necroscopy, it is considered unlikely that mortality would occur between 200 and 300 mg/kg. The anticipated LD50 would therefore be > 300 mg/kg, hence classified in Category 4.

Although not indicated in the report, for classification purposes for use in mixtures a LD50 cut-off value of 500 mg/kgbw is suggested.