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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
short-term repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has been assessed for the use in a category approach. According to the methodology and to the extent of available details, the study has been judged as reliable with restrictions.

Data source

Reference
Reference Type:
publication
Title:
THE VASCULAR REACTIONS IN EXPERIMENTAL ACUTE TARTRATE NEPHRITIS
Author:
H. T. KARSNER
Year:
1917
Bibliographic source:
Department of Pathology, School of Medicine, Western Reserve University, Cleveland, Ohio

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Subacute administration of substance by subcutaneous route to in vivo animals to evaluate repetaed dose toxicity
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(+)-tartaric acid
EC Number:
201-766-0
EC Name:
(+)-tartaric acid
Cas Number:
87-69-4
Molecular formula:
C4H6O6
IUPAC Name:
(2R,3R)-2,3-dihydroxybutanedioic acid
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
no data

Test animals

Species:
dog
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: intraperitoneal injection and subcutaneous injection
Vehicle:
not specified
Details on exposure:
It will be noticed that whereas in the second and third day animals the tartrate was administered subcutaneously, in the fifth day animals the dose was given intraperitoneally. This was because of the likelihood of necrosis and sloughing about the site of subcutaneous injections.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
5 days
Frequency of treatment:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
Tartrate nephritis was induced by subcutaneous/intraperitoneal injection of tartaric acid
The caffein in all cases was in the form of a 1% solution of the pure alkaloid, the strong saline was 5% NaCl solution, the adrenaline 1-1000 solution, the dog's urine filtered and undiluted. In every case the solutions were warmed and run into the femoral vein from a burette; the latter being washed out with 8 to 10 cc. 0.85 per cent salt solution. In the case of dogs A, C and 3, caffein solution was used in arbitrary doses of 2 cc., but in all other animals was given at the rate of 1 cc. per kilo. Strong saline was given at the rate of 5 cc. per kilo. Adrenalin was given in the arbitrary amount of 1 drop 1-1000 solution. Dog urine was given in arbitrary doses of 3 cc.
No. of animals per sex per dose:
In all, 32 dogs were used for this study including the normal controls.
The protocols of three normal controls follow. Three dogs were studied approximately twenty-four hours after poisoning, 3 dogs at forty-eight hours and 3 dogs after four days had elapsed. After each experiment thin blocks of kidney were fixed in Zenker's fluid, embedded in celloidin, cut and stained with hemalum and eosin.
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
no data
Sacrifice and pathology:
no data
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
Histological examination was made of the kidneys of 8 of the 9 animals reported above and varying degrees of degenerative and necrotic changes found in the tubular epithelium. The glomeruli were congested but no exudate was found in the subcapsular spaces. It would appear that the precipitate in the glomerular subcapsular space is not dependent upon the duration of the condition nor upon the mode of administration of the drug and that it is probably washed out in the course of active diuresis such as occurs in the physiological experiments.

Effect levels

open allclose all
Key result
Dose descriptor:
other: effects with tartrate nephritis
Based on:
other: caffein, saline solution, adrenalin, own dog's urine
Sex:
not specified
Basis for effect level:
other: During the second and third days of tartrate nephritis in dogs the vascular reactions of the kidney are practically normal except that caffein does not produce a diuretic effect equal to that seen in normal dogs.
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)
Key result
Dose descriptor:
other: effects with tartrate nephritis
Based on:
other: caffein, saline solution, adrenalin, own dog's urine
Sex:
not specified
Basis for effect level:
other: In the fifth day of tartrate nephritis the vascular reactions are somewhat more marked than normal and the diuretic effect of caffein is equal to that seen in normal animals.
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)
Key result
Dose descriptor:
other: effects with tartrate nephritis
Based on:
other: caffein, saline solution, adrenalin, own dog's urine
Sex:
not specified
Basis for effect level:
other: The study has shown no additional reasons for believing that the appearance of albuminous precipitate in the subcapsular space indicates an alteration in the functional capacity of the glomerulus, nor has the converse been proven.
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)
Key result
Dose descriptor:
other: effects with tartrate nephritis
Based on:
other: caffein, saline solution, adrenalin, own dog's urine
Sex:
not specified
Basis for effect level:
other: see 'Remark'
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)
Key result
Dose descriptor:
other: effects with tartrate nephritis
Based on:
other: caffein, saline solution, adrenalin, own dog's urine
Sex:
not specified
Basis for effect level:
other: The depressor substance of dog' s urine is not removed by the presence of tartrate nephritis, although it may be somewhat reduced either in quantity or in activity.
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)

Target system / organ toxicity

Key result
Critical effects observed:
not specified

Any other information on results incl. tables

4 dogs died before there was opportunity to study the vascular reactions and all showed marked necrosis of the epithelium of the convoluted tubules. One of these animals survived only eight hours after the injection of tartrate (intraperitoneally) yet showed marked necrosis in addition to the glomerular condition, one other survived twenty-one hours (after subcutaneous injection) one survived twenty-four hours (intraperitoneal injection) and one survived forty-eight hours (subcutaneous ·injection).

Applicant's summary and conclusion

Conclusions:
Dogs with tartrate nephritis showed normal vascular reactions in the first 3 days whereas at 5th day the vascular reactions were somewhat more marked than normal and the diuretic effect of caffein was equal to that seen in normal animals.
Executive summary:

Dogs with tartrate nephritis showed normal vascular reactions in the first 3 days whereas at 5th day the vascular reactions were somewhat more marked than normal and the diuretic effect of caffein was equal to that seen in normal animals.