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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-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
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

Constituent 1
Chemical structure
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 levelsopen allclose all
Sex:
female
Dose descriptor:
LD0
Effect level:
ca. 266 mg/kg bw
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)