N,N,N',N'-tetramethylhexamethylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

There is no information on the purity of test, the source and age of the animals, the period of acclimation, on housing and environmental conditions and on how often the clinical signs and mortality were checked.

GLP compliance:

no

Remarks:

GLP was not mandatory when the study was carried out

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethylhexamethylenediamine

EC Number:

203-842-9

EC Name:

N,N,N',N'-tetramethylhexamethylenediamine

Cas Number:

111-18-2

Molecular formula:

C10H24N2

IUPAC Name:

[6-(dimethylamino)hexyl]dimethylamine

Specific details on test material used for the study:

- Name of test material (as cited in study report):NIAX Catalyst C-210
- Purity: As supplied
- Physical state: transparent, pale yellow, non-viscous liquid

Test animals

Species:

rat

Strain:

other: Hllltop-Wi.tar albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 300 g
- Fasting period before study: Fasted overnight before dosing
- Diet (e.g. ad libitum): ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No information

Doses:

First test
0.125, 0.25, 0.5 and 1 mL/kg TMHD
Second test:
The acute oral test was repeated using a 5% (v/v) dilution in distilled water.
0.125, 0.25, 0.5, 0.71 and 1 mL/kg TMHD

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animal weights are recorded at days 0 (before dosing), 7 and 14 days (just prior to sacrifice).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weights

Statistics:

LD50's are calculated by the moving average method (Thompson, 1947).

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

0.42 mL/kg bw

Based on:

test mat.

Remarks on result:

other: All the females died in the highest dose group. 4/5 female rats died in the 0.5 mL/kg dose group and 2 female died in the 0.25 mL/kg dose group. The 0.125 mL/kg dose group was not considered relevant because the small volume were difficult to administer.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

336 mg/kg bw

Based on:

test mat.

Remarks on result:

other: relative density = 0.8

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

0.297 mL/kg bw

Based on:

test mat.

Remarks on result:

other: All the females died in the highest dose group. 4/5 female rats died in the 0.5 mL/kg dose group and 2 female died in the 0.25 mL/kg dose group. The 0.125 mL/kg dose group was not considered relevant because the small volume were difficult to administer.

Effect levels 4

Sex:

female

Dose descriptor:

LD50

Effect level:

238 mg/kg bw

Based on:

test mat.

Remarks on result:

other: relative density = 0.8

Mortality:

Undiluted test substance
At the highest dose level (1 mL/kg): 5/5 males died on day 1 and all females died on day 1..
At 0.5 mL/kg dose: 2 males died on day 1 and 1 male died on day 7. 3 females died on day 2 and one female died on day 3.
At 0.25 mL/kg: one male died on day 7. One female died on day 2 and the se second one on day 8.
At 0.125 mL/kg: one male died on day 2 and 2 males died on day 4. One female died on day 2 and 2 females died on day 3. However, due to the difficulties in administering this volume, this dose level was no considering when setting the LD50.
5% v/v dilution:
At the highest dose level (1 mL/kg): 3/5 males died on day 0 an 2/5 males died on day 1 and 3/5 females died on day 0 an 2/5 females died on day 1.
At 0.71 mL/kg dose: 3/5 males died on day 3 and 1 male died on day 4. No data reported or females.
At 0.5 mL/kg dose: No death was reported in males. 1 female died on day 2 and one female died on day 3.
At 0.25 mL/kg: No death was reported in males. 1 female died but the time is not reported.
At 0.125 mL/kg: All the animals survived.

Clinical signs:

other: Undiluted test material The following clinical signs were reported for males: 1.0 mL/kg dose group: sluggishness at 15 minutes. 0.5 mL/kg dose group: sluggishness at 20 minutes, red crusty discharge on nose and eye area at day 1 (one animal recovered

Gross pathology:

At gross pathology, the following findings were noted in the groups treated with the undiluted test material mottled and red lung (in male and females), red fluid In the stomach (in males and females), ulceration of the stomach, mucosa and gas or liquid-filled intestines (in females).
At gross pathology, the following findings were noted in the groups treated with the diluted test material pale red lungs stomach and lntestines filled with dark red liquid and with fluid in the thoracic cavity. Nothing remarkable was noted in the survivors.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Based an the results of thls study, the acute oral LD50 for TMHD in the rat should be considered to be 0.420 mL/kg (equivalent to 336 mg/kg) for males and 0.297 mL/kg (equivalent to 238 mg/kg) for females.

Executive summary:

Groups of five Hilltop-Wistar 344 rats/sex/dose were administered a single dose of the undiluted test material by gavage at the following doses 0.125mL/kg, 0.25, 0.5 and 1 mL/kg NIAX Catalyst C-210. The animals were observed for mortality, clinical signs during a 14-day observation period. Body weights were recorded on days 0, 7 and 14 post dosing. Gross pathology was carried out on all animals. All female and male rats died in the 1 mL/kg. 3/5 males and 4/5 males died in the 0.5 mL/kg group. At 0.25 mL/kg, 1/5 male and 2/5 females were reported dead. 3/5 males and 3/5 females died in the 0.1 mL/kg treated group. However this last dose group was not considered in the derivation of the LD50 due to difficulties in administering such a low dosage. Based on the results of this study, the acute oral LD50 for TMHD in the rat should be considered to be 0.420 mL/kg (equivalent to 336 mg/kg bw) for males and 0.297 mL/kg (equivalent to 238 mg/kg bw) for females. It is therefore concluded that the substance classified as Acute Tox Cat. 3 under Regulation (EC) No 1272/2008 and is assigned the hazard statement H301 "Toxic if swallowed".