N,N,N',N'-tetramethylethylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 to 27 June 2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

No evidence of GLP compliance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

no

Remarks:

The report was signed by the Study Director declaring that the methods, results and data in the report relected the procedures used and the raw data collected during the study.

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethylethylenediamine

EC Number:

203-744-6

EC Name:

N,N,N',N'-tetramethylethylenediamine

Cas Number:

110-18-9

Molecular formula:

C6H16N2

IUPAC Name:

[2-(dimethylamino)ethyl]dimethylamine

Test material form:

liquid

Details on test material:

clear, colourless to pale yellow

Specific details on test material used for the study:

BULAB 600
Lot number 46903
Clear, colourless to light yellow liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Source: Harlan
Housing: Individually in suspended stainless steel cages with mesh floors.
Photoperiod: 12 hours light/dark cycle
Food: Harlan Teklad Global 16% protein rodent diet 2016
Water: Filtered tap water, ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Animals were fasted overnight. Eight female animals were tested. Test material was administered as received. The first animal was administered 175 mg/kg bw test material by oral gavage. Seven additional females were dosed at levels of 175, 550 or 2000 mg/kg bw using the Up and Down procedure. Doses were administered using a stainless steel ball tipped gavage needle. After administration, animals were returned to their cages. Food was replaced 3-4 hours after dosing.

Doses:

175, 550 or 2000 mg/kg bw

No. of animals per sex per dose:

175 mg/kg bw (3 females); 550 mg/kg bw (4 females); 2000 mg/kg bw (1 female)

Control animals:

no

Details on study design:

All animals were observed for mortality, signs of gross toxicity and behavioural changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Day 14 (termination) following dosing or after death. Animals were euthanised by carbon dioxide inhalation at termination. A gross necropsy was performed on all animals.

Statistics:

Not required

Results and discussion

Preliminary study:

Not performed

Effect levels

Key result

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

550 mg/kg bw

Based on:

test mat.

95% CL:

> 196.4 - < 884

Mortality:

No animals died at the lowest dose of 175 m/kg bw. Three of the four animals died at the mid dose of 550 mg/kg bw within one day of administration. At the highest dose of 2000 mg/kg bw, the single animal died within one hour of administration.

Clinical signs:

other: At the low dose of 175 mg/kg bw, animals appeared healthy with the exception of ano-genital staining and reduced faecal volume which was noted for one animal on Day 1. At the mid dose of 550 mg/kg bw, oral and ocular discharge, irregular respiration, hyp

Gross pathology:

No abnormalities were noted for the animals dosed with 175 mg/kg bw. Following gross necropsy of the decedents at 550 mg/kg bw, discoloration of the lungs, liver, stomach, intestines and/or spleen and distention of the stomach and intestines were observed. No gross abnormalities were noted for the euthanised animal necropsied at the conclusion of the 14-day observation period. Gross necropsy of the decedent at 2000 mg/kg bw revealed discoloration of the lungs, stomach, spleen, liver and intestines and distention of the intestines.

Any other information on results incl. tables

Clinical observations

Observations	175 mg/kg bw	550 mg/kg bw	2000 mg/kg bw
Ano-genital staining	1/3	2/4	0/1
Reduced faecal volume	1/3	1/4	0/1
Irregular respiration	0/3	3/4	0/1
Hypoactivity	0/3	4/4	0/1
Ataxia	0/3	4/4	0/1
Ocular discharge	0/3	2/4	0/1
Nasal discharge	0/3	1/4	0/1
Oral discharge	0/3	1/4	0/1
Hunched posture	0/3	2/4	0/1
Mortality	0/3	3/4	1/1

Necropsy observations

Observations	175 mg/kg bw	550 mg/kg bw	2000 mg/kg bw
Red colouration of lungs	0/3	3/4	1/1
Red colouration of stomach	0/3	2/4	1/1
Red colouration of intestines	0/3	2/4	1/1
Red colouration of spleen	0/3	1/4	1/1
Red colouration of liver	0/3	1/4	0/1
Mottled liver	0/3	0/4	1/1
Distention of stomach	0/3	2/4	0/1
Distention of intestines	0/3	3/4	1/1

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of BULAB 600 was estimated to be 550 mg/kg bw with a 95% confidence interval of 196.4-884 mg/kg bw.

Executive summary:

An acute oral toxicity study was conducted with BULAB 600 (TMEDA) based on the Up and Down method (OECD TG425). Sprague Dawley rats were dosed with a starting dose of 175 mg/kg bw: there were no mortalities and gross pathology findings, although some clinical findings (ano-genital staining and reduced faecal volume) were noted in a single animal on Day 1. At 550 mg/kg bw, three of the four animals died within 1 day of dosing. Decedent animals dosed with 550 mg/kg bw showed clinical signs prior to death of oral and ocular discharge, irregular respiration, hypoactivity, hunched posture, ataxia and ano-genital staining. The surviving rat dosed with 550 mg/kg bw exhibited nasal discharge, hyopactivity, ano-genital staining, ataxia and reduced faecal volume following administration but recovered from these symptoms by Day 3. This animal appeared healthy for the remainder of the observation period. A single animal dosed with 2000 mg/kg bw died within 1 hour of dosing; no clinical signs were observed. Discoloration of the lungs, liver, stomach, intestines and/or spleen and distention of the stomach and/or intestines were observed in decedent animals at 550 and 2000 mg/kg bw. No gross abnormalities were noted for the euthanised animal dosed with 550 mg/kg bw necropsied at the conclusion of the 14-day observation period. The LD50 of the test material was estimated to be 550 mg/kg bw with a 95% confidence interval of 196.4 -884 mg/kg bw.