N,N-dimethylglycinium chloride

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication

Data source

Reference

Reference Type:

publication

Title:

Acute Oral Toxicity (LD50) Study in the Rat with Neutralized N, N Dimethylglycine Hydrochloride

Author:

R. V. Kendall and S. M. Glaza

Year:

1992

Bibliographic source:

International Journal of Toxicology, Volume: 1 issue: 3s, page 198, 1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Acute oral toxicity of N,N-dimethylglycinium chloride (2491-06-7) in rat.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethylglycinium chloride

EC Number:

219-648-2

EC Name:

N,N-dimethylglycinium chloride

Cas Number:

2491-06-7

Molecular formula:

C4H9NO2.ClH

IUPAC Name:

2-(dimethylamino)acetic acid hydrochloride

Details on test material:

SMILES:Cl_CN(C)CC(O)=O

Specific details on test material used for the study:

- Name of test material (as cited in study report): N,N-dimethylglycinium Hydrochloride
- Molecular formula (if other than submission substance): C4H10ClNO2
- Molecular weight (if other than submission substance): 139.581 g/mol
- Substance type: Organic

Test animals

Species:

rat

Strain:

other: Crl:CD® BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: young adult albino rats were taken for the study.
- Weight at study initiation: No data
- Fasting period before study: 17 to 20 hours
- Housing:
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 3000 and 5000 mg/kg for female and 5000 and 6500 mg/kg for male
- Amount of vehicle (if gavage): 20.00 ml/Kg
- Justification for choice of vehicle: distilled water
- Lot/batch no. (if required):not specified
- Purity:not specified

MAXIMUM DOSE VOLUME APPLIED:not specified

DOSAGE PREPARATION (if unusual): Test material was mixed in distilled water, pH then adjusted to 7.4 using a NaOH solution and administered at a dose volume of 20.00 ml/Kg for each animal.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:not specified

Doses:

Females – 3000, 5000, 7000 mg/kg
Male – 5000, 6000 and 7000 mg/kg

No. of animals per sex per dose:

Total = 30
5 female -3000 mg/kg
5 female - 5000 mg/kg
5 female - 7000 mg/kg
5 male - 5000 mg/kg
5 male - 6000 mg/kg
5 male - 7000 mg/kg

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed for clinical signs and mortality at 1, 2.5 and 4 hours after test material administration. Surviving animals were observed daily thereafter for 14 days for clinical signs and twice daily for mortality.
Weighing: All animals were weighed just before test material administration and again at Day 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: The animals were observed for clinical signs, body weight and gross pathology were examination.

Statistics:

A Computer Program for Estimating LD50 and its Confidence Limits Using a Modified Behrens-Reed-Muench Cumulant Method

Results and discussion

Preliminary study:

not specified

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 400 mg/kg bw

Based on:

test mat.

95% CL:

4 500 - 6 400

Remarks on result:

other: 50 5 mortality observed

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

5 800 mg/kg bw

Based on:

test mat.

95% CL:

5 100 - 6 600

Remarks on result:

other: 50 % mortality observed

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

3 900 mg/kg bw

Based on:

test mat.

95% CL:

3 000 - 5 000

Remarks on result:

other: 50 % mortality observed

Mortality:

When treated with 7000 mg/kg bw, all male and female died within 2.5 to 4 hours.
When treated with 6000 mg/kg bw, 3 male died.
When treated with 5000 mg/kg bw, all female rats were died.
When treated with 3000 and 5000 mg/kg bw, no mortality were observed in male and female rats.

Clinical signs:

other: Hypoactivity, ataxia, diarrhea, brown-stained abdomen, red-stained face, dyspnea, circling movements, prostration and absence of pain reflex in rats were observed in treated rats.

Gross pathology:

Test substance centred around the gastrointestinal tract were observed in dead animals and no gross lesions were observed in the animals which surviving to the termination of the experimental phase.

Any other information on results incl. tables

 Table – Acute oral toxicity in rats

DOSE AS DMG FREEBASE G/KG	^1DOSE AS DMG FREEBASE G/KG	NUMBER DOSED	CUMULATIVE MORTALITY
			HOUR			DAY
			1	2.5	4	1	2	3	4	5	6	7-14
3	2.3	5F	0	0	0	0	0	0	0	0	0	0
5	3.8	5M	0	0	0	0	0	0	0	0	0	0
5	3.8	5F	0	0	0	5	5	5	5	5	5	5
6	4.6	5M	0	0	0	2	3	3	3	3	3	3
7	5.3	5M	0	1	5	5	5	5	5	5	5	5
7	5.3	5F	0	3	4	5	5	5	5	5	5	5

 

1 - Dose reflects content as DMG freebase equivalent calculated at 75.9% of the hydrochloride level.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was considered to be 5400 mg/kg bw (95% confidential limit 4500 - 6400 mg/kg) for males and females, 5800 mg/kg (95% confidential limit = 5100 – 6600 mg/kg) for males and 3900 mg/kg (95% confidential limit = 3000 - 5000 mg/kg) for females, when Crl:CD® BR male and female rats were treated with N,N-dimethylglycinium chloride orally by gavage.

Executive summary:

In a acute oral toxicity study, groups of five female and five male young adult albino Crl:CD® BR rats were treated with N,N-dimethylglycinium chloride at the concentration of 3000, 5000, 7000 mg/kg in Females and 5000, 6000 and 7000 mg/kg in Males.Each dose of test material was mixed in distilled water, pH then adjusted to 7.4 using a NaOH solution and administered at a dose volume of 20 ml/kg for each animal by gavage route.Animals were fasted17 to 20 hours prior to dosing. Water wasfully available at all times.The animals were observed for clinical signs and mortality at 1, 2.5 and 4 hours after test material administration. Surviving animals were observed daily thereafter for 14 days for clinical signs and twice daily for mortality. All animals were weighed just before test material administration and again at Day 7 and 14. All animals, whether dying during the study or euthanatized at study termination, were subjected to a gross necropsy examination and all abnormalities were reported. All male and female died within 2.5 to 4 hours at 7000 mg/kg bw, 3 male died at 6000 mg/kg bw, all female rats were died at 5000 mg/kg bw and no mortality were observed in male and female rats at 3000 and 5000 mg/kg bw. Hypoactivity, ataxia, diarrhea, brown-stained abdomen, red-stained face, dyspnea, circling movements, prostration and absence of pain reflex in rats were observed in treated rats. Weight gain was observed in animals which survive to the end of the observation period.Test substance centred around the gastrointestinal tract were observed in dead animals and no gross lesions were observed in the animals which surviving to the termination of the experimental phase. Therefore,LD50 was considered to be 5400 mg/kg bw (95% confidential limit 4500 - 6400 mg/kg) for males and females,5800 mg/kg (95% confidential limit = 5100 – 6600 mg/kg) for males and 3900 mg/kg (95% confidential limit = 3000 - 5000 mg/kg) forfemales, when Crl:CD® BR male and female rats were treated with N,N-dimethylglycinium chloride orally by gavage.