Sodium calcium edetate

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Old study, pre-GLP and pre-guideline. Sufficient details available for evaluation.

Data source

Reference

Reference Type:

publication

Title:

Hydropic degeneration of the rat kidney after administration of Na2[Ca-EDTA] and Na3[Ca-DTPA]

Author:

Weber KM

Year:

1970

Bibliographic source:

Virchows Arch. Abt. B Zellpathol. 5, 39-59

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Examination of kidney effects following repeated ip or sc injections

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium calcium edetate

EC Number:

200-529-9

EC Name:

Sodium calcium edetate

Cas Number:

62-33-9

Molecular formula:

C10H12CaN2O8.2Na

IUPAC Name:

calcium disodium 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate

Test material form:

other: aqueous solutions

Details on test material:

no data

Test animals

Species:

rat

Strain:

other: Heiligenberg Inbred strains

Sex:

male

Administration / exposure

Route of administration:

other: intraperitoneal or subcutaneous

Vehicle:

physiological saline

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Daily injections or every 3rd day

Frequency of treatment:

Variable up to 32 times

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 2, 4 and 8 mmol/kg bw/day (1st study), 2.5 mmol/kg bw/day (2nd study)

No. of animals per sex per dose:

5 (in total 782 test animals and 245 control animals used)

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

4 other: mmol/kg bw/day

Based on:

test mat.

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

The lesions induced in the kidneys of the rat by 1, 2, 4 and 8 mmol Na2[Ca-EDTA]/kg bw/day were compared with those induced by Na3[Ca-DTPA]. The following results were obtained: 1. The well-known renal alterations caused by chelates include more than a hydropic degeneration of the proximal convoluted tubule. Iysosomes probably partake in the development of that degeneration. 2. The degeneration of the epithelium of the proximal tubules, typical of the action of EDTA doses <8 mmol, cannot be considered as important in causing death. 3. None of the renal effects as seen histologically - such as alteration of the straight portion of the proximal tubules (typical of the action of DTPA doses >1 mmol and of 8mmol EDTA, alteration of glomeruli, distal tubules, and collecting ducts, tubulorhexis, hyaline casts and others - can be correlated directly with mortality. It is questionable whether the kidney is the critical organ in chelate toxicity. 4. This conclusion is corroborated by studying the effects of chelate as they develop. In the pertinent experiment the kidney as well as duodenum, liver, and adrenal cortex were studied 48 and 72 hr, after the injection of 2.5 mmol/kg of chelates. The results showed that the lesions of the straight portion of the proximal tubules, typical of the action of DTPA, became

manifest after a latent period but in general regenerate quickly.