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Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment

Data source

Reference
Reference Type:
publication
Title:
Effect of sodium etidronate in adult cats
Author:
Jowsey, J, Holley, KE and Linman, JW
Year:
1970
Bibliographic source:
J Lab Clin Invest 76, 126 - 133

Materials and methods

Type of study / information:
Effects on bone.
Test guideline
Qualifier:
no guideline followed
GLP compliance:
no
Remarks:
pre-GLP

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
EC Number:
701-238-4
Cas Number:
29329-71-3
Molecular formula:
HEDP-2Na C2H6Na2O7P2 HEDP-3Na C2H5Na3O7P2
IUPAC Name:
Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
Test material form:
not specified
Details on test material:
CAS No. 7414-83-7
Described as sodium etidronate, presumed disodiumethane-1-hydroxy-1,1-diphosphonate, source and purity not stated.
No further information.

Results and discussion

Any other information on results incl. tables

Six of seven cats given 500 mg/kg sodium HEDP (nominal) died following 4 week treatment. Increased serum creatinine noted in most decedents.

Histopathological examination of the kidney from cats given 50 or 500 mg/kg bw/day (nominal) for 6 weeks showed acute and chronic inflammatory changes affecting both interstitial and tubular elements (no further details). No renal changes were noted in cats given 25 mg/kg bw/day (nominal) for 6 months. 

Bone sections demonstrated a significant (P<0.01) increase in osteoid tissue width in cats given 500 (2.4-fold) or 50 (1.7-fold) mg/kg bw/day (nominal) for 6 weeks. Similar increases (reported as 2) were present in cats given 1 - 25 mg/kg bw/day (nominal) for 6 months.

The authors note that the effect of sodium HEDP on one appears to be minimal at doses 25 mg/kg bw/day (nominal) for 6 months, however (based upon the limited evidence presented in this paper) a comparable effect also appeared to be present in the low dose animals. Overall, therefore, these results suggest that 1 mg/kg bw/day (nominal) over 6 months is a
LOAEL for increased osteoid activity in the cat, however, the reliability of the underlying data is considered low.

Applicant's summary and conclusion

Conclusions:
In a study investigating the effects on bone (reliability score 4), not conducted according to any OECD Test Guideline and pre-GLP, a LOAEL of 1 mg/kg bw/day was determined based on increased osteoid activity in the cat.