N,N,N',N'-tetramethyltrimethylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (limited characterisation of test substance, reduced documentation of test animal welfare)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(limited documentation on test substance and test animals)

Principles of method if other than guideline:

BASF-Test: The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.
Test groups consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. 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.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethyltrimethylenediamine

EC Number:

203-818-8

EC Name:

N,N,N',N'-tetramethyltrimethylenediamine

Cas Number:

110-95-2

Molecular formula:

C7H18N2

IUPAC Name:

N,N,N',N'-tetramethyltrimethylenediamine

Details on test material:

- Name of test material (as cited in study report): Tetramethyl-propylendiamin
- Analytical purity: no data
- Physical state: liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gassner
- Mean weight at study initiation: 189 g (males); 164 g (females)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 8 %

MAXIMUM DOSE VOLUME APPLIED: ca. 15 mL/kg bw

Doses:

400, 500, 640, 800, 1000, 1250 µL/kg bw (312, 390, 500, 624, 780, 975 mg/kg bw - based on the density d=0.78 g/cm³)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observation: daily
- Frequency of weighing: days 0, 3, 7 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

0.8 mL/kg bw

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

624 mg/kg bw

Based on:

test mat.

95% CL:

> 500 - < 780

Remarks on result:

other: based on the density d=0.78 g/cm³

Mortality:

975 mg/kg: 9/10 (2 males and 4 females died within 6 h post application. 3 further males died within 24 h post application.)
780 mg/kg: 7/10 (1 male and 2 females died within 24 h post application. 3 further males and 1 further female died within 7 days post application.)
624 mg/kg: 4/10 (1 female died within 24 h. 2 further females and 1 male died within 7 days.)
500 mg/kg: 1/10 (1 male died within 48 h.)
390 mg/kg: 1/10 (1 female died within 14 days.)
312 mg/kg: 1/10 (1 female died within 48 h.)

Clinical signs:

other: - 975 and 780 mg/kg: immediately after application: accelerated respiration; 1 h post application: abdominal position, mouth discharge, chewing reflex, in some animals dyspnoea; 3 h post application: red smeared snouts and ruffled fur; 2 days post applica

Gross pathology:

Animals that died during observation period: acute passive hyperemia; acute dilatation of the heart; glandular stomach reddened diffusely; isolated ulcerations; diarrhetic contents of the intestines; acinar pattern of the liver

Sacrificed animals: 975 mg/kg: 1x thickened forestomach-epithelium

Any other information on results incl. tables

Mortality:

Dose: (mg/kg)	Gender	1 h	24 h	48 h	day 7	day 14
975	male	0/5	5/5	5/5	5/5	5/5
975	female	0/5	4/5	4/5	4/5	4/5
780	male	0/5	1/5	3/5	4/5	4/5
780	female	0/5	2/5	2/5	3/5	3/5
624	male	0/5	0/5	0/5	1/5	1/5
624	female	0/5	1/5	1/5	3/5	3/5
500	male	0/5	0/5	1/5	1/5	1/5
500	female	0/5	0/5	0/5	0/5	0/5
390	male	0/5	0/5	0/5	0/5	0/5
390	female	0/5	0/5	0/5	0/5	1/5
312	male	0/5	0/5	0/5	0/5	0/5
312	female	0/5	0/5	1/5	1/5	1/5

 

Weight (g):

Dose (mg/kg)	Gender	day 0	day 3	day 7	day 13
975	male	168	-	-	-
780	male	192	171	206	246
624	male	186	164	184	211
500	male	194	175	211	231
390	male	180	174	207	210
312	male	193	200	229	236
975	female	163	143	158	159
780	female	163	149	157	172
624	female	165	154	149	231
500	female	164	147	173	173
390	female	165	146	150	170
312	female	166	178	168	181

Harmful if swallowed. There is indication that the test substance causes local irritation to exposed tissue.

 

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

The Acute oral toxicity of Tetramethylpropylendiamine (TMPDA) was evaluated in rats according an internal BASF method, which in principle is comparable to the OECD Guideline 401.

A test group consisting of 5 Sprague-Dawley rat/sex was treated by single gavage application with an aqueous solution of the test substance. 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. The LD50 value was estimated on the basis of the observed mortalities.

At 975 mg/kg, 2 males and 4 females died within 6 h after treatment. 3 further males died within 24 after treatment.

At 780 mg/kg, 1 male and 2 females died within 24 h after treatment. 4 males and 3 females died within 7 days after treatment.

At 624 mg/kg, 1 female died within 24 h. 3 females and 1 male died within 7 days.

At 500 mg/kg, 1 male died within 48 h.

At 390 mg/kg, 1 female died within 14 days. 312 mg/kg: 1 female died within 48 h.

Under these experimental conditions, the oral LD50 of TMPDA is 624 mg/kg in rats.