N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data from published paper. Reported sufficiently to be able to make a judgement on the quality of the data and the reliabiity

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Evaluation of LD50 of some polyaminocarboxylic acids used as chelating drugs in metal intoxication

Author:

Srivastava RC, Dwivedi PP, Behari JR, Athar M

Year:

1986

Bibliographic source:

Toxicology letters, volume 32, pages 37-40

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute toxicity assessed using intraperitoneal administration of test compound.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

EC Number:

200-652-8

EC Name:

N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

Cas Number:

67-43-6

Molecular formula:

C14H23N3O10

IUPAC Name:

2-[bis({2-[bis(carboxymethyl)amino]ethyl})amino]acetic acid

Constituent 2

Reference substance name:

Diethylenetriaminepentaacetic acid

IUPAC Name:

Diethylenetriaminepentaacetic acid

Details on test material:

DTPA acid (pure) obtained from Sigma Chemicals, U.S.A)

Test animals

Species:

rat

Strain:

other: Albino

Sex:

female

Details on test animals or test system and environmental conditions:

Female albino rats weighing 150 - 200g maintained in an air conditioned room with a temperature of 20-25 degrees Celcius, and an average humidity of 45-55%.
Pellet feed and tap water provided ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: 0.9% sodium chloride solution, pH adjusted to 7.0 +/- 0.2 with NaOH or HCl

Details on exposure:

Dosing solutions were prepared in 0.9% sodium chloride solution and pH adjusted to 7 +/- 0.2 using either NaOH or HCl. Single doses (10ml/kg bw) were injected intraperitoneally.

Doses:

266, 400, 500, 600, 700, 1000 mg/kg bw

No. of animals per sex per dose:

10 female rats per dose

Control animals:

no

Details on study design:

After administration of test compound the rats were observed for 14 days. On the last day all surviving animals were killed and necrospied. All animals dying during the course of the obsevation period were necropsied. Gross examination of the viscera and organs only.

Statistics:

LD50 value determined using Probit analysis

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD0

Effect level:

ca. 266 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 587 mg/kg bw

95% CL:

> 475.6 - < 724.4

Mortality:

Dose (mg/kg) Mortality
266 0/10
400 1/10
500 2/10
600 4/10
700 7/10
1000 10/10

Clinical signs:

Administration of the test material caused irritation, convulsions and aggressiveness.

Body weight:

no data

Gross pathology:

Necropsy revealed congestion of the liver, kidney and lungs.

Other findings:

No data is given as to which animals displayed these effects, nor whether there was a dose response.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:

Under the conditions of the study, the LD50 of DTPA to female albino rats was 587 mg/kg (475.6-724.4)

Executive summary:

The LD50 of the following metal-binding chelating drugs, EDTA, DTPA, HEDTA, CDTA and TTHA was evaluated in terms of mortality after intraperitoneal administration and under the conditions of the study, the LD50 of DTPA to female albino rats was 587 mg/kg (475.6-724.4)