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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1960
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP, short documentation. Number of animals not given, purity not specified

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1960
Report date:
1959

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
1) Rats were fed by gavage a solution containing approximately 50 mg radioactive adipic acid . Rats were immediately placed in individual metabolism chambers for 24 hours for collection of respiratory carbon dioxide. Urine was collected during the whole experimental procedure. 2) Animals were fed by gavage a solution containing approximately 100 mg radioactive adipic acid labeled in the C-1 position and 400 mg glucose. Animals were sacrificed after two hours and livers were analyzed for glycogen. 3) Animals were fed by gavage a solution containing approximately 50 mg radioactive adipic acid and then injected intraperitoneally with 2 ml of 0.5 M sodium malonate. Urine was collected for 24 hours. The distribution of radioactivity in the breath and urine was monitored.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Adipic acid
EC Number:
204-673-3
EC Name:
Adipic acid
Cas Number:
124-04-9
Molecular formula:
C6H10O4
IUPAC Name:
Hexanedioic acid
Test material form:
not specified
Details on test material:
IUCLID4 Test substance: purity not specified
Radiolabelling:
not specified

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
/

Administration / exposure

Route of administration:
other: no data
Vehicle:
not specified
Details on exposure:
/
Duration and frequency of treatment / exposure:
/
Doses / concentrations
Remarks:
Doses / Concentrations:
/
No. of animals per sex per dose / concentration:
/
Control animals:
not specified
Positive control reference chemical:
/
Details on study design:
/
Details on dosing and sampling:
/
Statistics:
/

Results and discussion

Preliminary studies:
/

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
other: up to 70 % of the radioactivity was exhaled as C02 in 24 h. In the urine the following radioactive metabolic products were identified: urea, glutamic acid, lactic acid, beta-ketoadipic acid, citric acid and adipic acid. The tissue showed ve
Test no.:
#2
Toxicokinetic parameters:
other: When glycogen formation in the liver was increased by oral administration of glucose together with radioactive adipic acid, a high concentration of glycogen was isolated which was radioactive
Test no.:
#3
Toxicokinetic parameters:
other: Radioactive succinic acid as well as radioactive adipic acid was obtained from the urine of these rats, indicating that adipic acid undergoes b-oxidation.

Any other information on results incl. tables

RS-Freetext: Experiment 1): up to 70 % of the radioactivity was exhaled as C02 in 24 h. In the urine the following radioactive metabolic products were identified: urea, glutamic acid, lactic acid, beta-ketoadipic acid, citric acid and adipic acid. The tissue showed very little radioactivity. Similar results were obtained with adipic acid labeled in the 1-C or 2-C position. Experiment 2) When glycogen formation in the liver was increased by oral administration of glucose together with radioactive adipic acid, a high concentration of glycogen was isolated which was radioactive; no further data. Experiment 3) Radioactive succinic acid as well as radioactive adipic acid was obtained from the urine of these rats, indicating that adipic acid undergoes b-oxidation. Experiment 4) In order to accumulate acetate in the urine rats were fed with gamma-phenyl-alpha-aminobutyric acid. The presence of radioactive acetyl-gamma-phenyl-alpha-aminobutyric provided evidence that acetate is a metabolite of adipic acid. Experiment 5) In the presence of adipic acid radioactive citric acid was formed, suggesting that carbon dioxide interacts with a metabolite of adipic acid.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no data