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Description of key information

In an acute oral toxicity study, the LD50 of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was 1669 (1249-2086) mg/kg for male and female rats. The most notable clinical abnormalities observed included a decrease in spontaneous activity, dyspnea, coma and body weight loss. Reddish or black colouration of the digestive tract, spleen and/or liver was observed in the animals found dead.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, OECD guideline n° 401 (1987 February 24th)
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: ICO: OFA-SD (IOPS Caw) supplied by Iffa Crédo, 69210 L'Arbresle, France
- Age at study initiation: approximalety 6 weeks
- Weight at study initiation: males: 184+/-5g, females 152+/-7g
- Fasting period before study: 18 hours before administration
- Housing: 5 animals of the same sex per cage during study
- Diet (e.g. ad libitum): ad libitum pellet diet "Rats-Mice sustenance ref. A04 C" (U.A.R. 91360 Villemoisson-sur-Orge)
- Water (e.g. ad libitum): ad libitum tap water filtered by a 0,22µ filter membrane (Société Millipore, 78140 Vélizy, France)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 50+/-20%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To: 1991-04-23
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: volume taking into consideration that the specific gravity (SG) of the test substance was 0.88.
Doses:
1000, 2000, 3000 mg/kg
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs checked once daily, animals weighted on day 5, 8 and 15
- Necropsy of survivors performed: yes, necropsy on all animals.
- Other examinations performed: Macroscopic examination on digestive track, heart, kidneys, libver, lungs, pancreas, spleen and any other organ with obvious anormalities. No histological examination was performed.
Statistics:
LD50 calculated according to a Probit analysis, Finney's method published by E. Weber and Bliss' method.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 669 mg/kg bw
95% CL:
1 249 - 2 086
Sex:
female
Dose descriptor:
LD50
Effect level:
1 545 mg/kg bw
95% CL:
690 - 2 379
Sex:
male
Dose descriptor:
LD50
Effect level:
1 907 mg/kg bw
95% CL:
467 - 2 273
Remarks on result:
other: 90% CL (not 95 %)
Mortality:
1000mg/kg: 10% (1 female found dead on day 7)
2000mg/kg: 60%
3000mg/kg: 100%
Clinical signs:
other: 1000mg/kg: hypokinesia bewteen 15 minutes and 6 hours 2000mg/kg: sedation, hypokinesia, dyspnea between 15 minutes and 6 hours, accompanied by tremors in 2 animals after 4 hours and coma for 1 animal after 6 hours. Hypokinesia persited therafter in a few
Gross pathology:
1000mg/kg: no apparent abnormalities observed
2000mg/kg: 1 female found dead on day 1, dark reddinsh stomach and intestines
2000mg/kg: 1 males found dead on day 1, dark stomach and black spleen
3000mg/kg: 2 males and 3 females on day 1, dark reddish stomach and intestineswith black liver and spleen.
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of DIMETHYLDIPROPYLENETRIAMINE administered by oral route in rats was
- males, 1907 (467 - 2273) mg/kg with 90% confidence interval limits,
- females, 1545 (690 - 2379) mg/kg with 95% confidence interval limits,
- combined, 1669 (1249 - 2086) mg/kg with 95% confidence interval limits.
Executive summary:

The acute oral toxicity of Dimethyldipropylenetriamine was evaluated in rats according to OECD N°401 guideline. The test item was administered by oral route (gavage at 1000, 2000 and 3000 mg/kg) to groups of 10 Sprague-Dawley rats (5 males and 5 females). Animals were observed for 14 days.

100% mortality was observed for the high dose group on day 1 ; after administration animals showed sedation, lateral recumbency, piloerection and coma. These clinical signs were less severe in 2000 mg/kg group, althought 60% mortality was observed on day 5. The low dose group showed hypokinesia after treatment but only 10% mortality was observed. Under these experimental conditions, the oral LD50 of the test item is 1669 (1249 - 2086) mg/kg with 95% confidence interval limits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 669 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Test type:
standard acute method
Species:
rat
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral route

The acute oral toxicity of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was evaluated in rats according to OECD N°401 guideline (Clouzeau, 1991). The test item was administered by oral route (gavage at 1000, 2000 and 3000 mg/kg) to groups of 10 Sprague-Dawley rats (5 males and 5 females). Animals were observed for 14 days. 100% mortality was observed for the high dose group on day 1; after administration animals showed sedation, lateral recumbency, piloerection and coma. These clinical signs were less severe in 2000 mg/kg group, althought 60% mortality was observed on day 5. The low dose group showed hypokinesia after treatment but only 10% mortality was observed. Under these experimental conditions, the oral LD50 of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine is 1669 (1249 - 2086) mg/kg with 95% confidence interval limits.

In a study conducted according to a method which in principle is comparable to the OECD Guideline 401 (BASF, 1991), a test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. At 2000 mg/kg, all animals died within 24 h, 1 female died within 48 h at 681 mg/kg, and 1 female died within 14 days at 200 mg/kg. The acute LD50 is >681 and <2000 mg/kg bw under the conditions of this study.


Justification for selection of acute toxicity – oral endpoint
Key study

Justification for classification or non-classification

Acute oral toxicity:

The oral LD50of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was 1669 mg/kg in rats. In accordance with Regulation (EC) No 1272/2008, N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine shall be classified as Acute Tox. 4 (Hazard statement: H302; Harmful if swallowed) and in accordance with Annex VI of Commission Directive 2001/59/EC, N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine shall be classified as being harmful if swallowed (R22).

Acute inhalation toxicity:

Data lacking.

Acute dermal toxicity:

Data lacking.