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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well described following scientific principles. No GLP. No data on purity.

Data source

Reference
Reference Type:
publication
Title:
Bio-distribution in rats of some salicylates with low gastric ulcerogenicity.
Author:
Rainsford KD, Schweitzer A, Green P et al
Year:
1980
Bibliographic source:
Agents and Actions, 10(5), 457-464.

Materials and methods

Objective of study:
distribution
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The distribution and metabolism of radioactively labelled test substance was investigated using whole body autoradiography and chemical analyses following oral administration.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: salicylic acid (SA)
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tierfarm, Tuttlingen, FRG
- Age at study initiation: no data
- Weight at study initiation: 100-130 g
- Fasting period before study: no data
- Housing: no data
- Individual metabolism cages: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sterile saline
Details on exposure:
Male Sprague-Dawley rats were inoculated with 0.05 ml 2% W/v carrageenan in sterile saline in the left rear paws to elicit an acute (local) inflammatory reaction. An injection of 0.05 ml sterile saline into the right rear paw served as control. The animals were then dosed orally with 1 ml aqueous fine suspensions of the radioactively labelled salicylic acid which were prepared immediately beforehand to minimize degradation.
Duration and frequency of treatment / exposure:
180 minute(s)
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: 10 and 100 mg/kg
No. of animals per sex per dose:
no data
Control animals:
not specified
Positive control:
no data
Details on study design:
- Dose selection rationale: no data
Details on dosing and sampling:
Blood samples (50-100 µl) were collected from one of the tail veins at 10 and 60 min after dosing and finally (on termination under ether anaesthesia at 180 min) from one of the carotid arteries or veins. The blood samples were assayed for total radioactive content following total combustion. After collection of the final blood sample the rats were bled as nearly as possible to completion, the carcasses shaved and rapidly frozen in a hexane-dry ice mixture. Whole body autoradiography was then prepared.
Statistics:
Nostatistics were performed

Results and discussion

Preliminary studies:
No preliminary studies were performed.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Following oral administration of radioactively labelled salicylic acid, the test substance was found in blood. The results are essentially qualitative because the varying dose levels employed were adjusted to account for the specific activity of the substance.
Details on distribution in tissues:
Salicylic acid was found in the stomach, liver, kidney lungs, bone marrow, intestine, inflamed paws and spleen.
Details on excretion:
not examined

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Small quantities of salicylic acid and 2,5-dihydroxybenzoic acid were present in the blood of rats dosed with salicylic acid.

Any other information on results incl. tables

The methyl ester of ASA (AME) was distributed in vivo very similarly to that observed with ASA and salicylic acid.AMEis rapidly demethylated following absorption from the stomach and is subsequently converted to ASA and salicylate. Salicylate is the main metabolite produced from both AMEand ASA, which specifically accumulates in inflamed tissues.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Under the conditions of this test, after oral administration salicylic acid passed into the blood and was distributed into several organs of the body.
Executive summary:

In this study (Rainsford et al., 1980), bio-distribution in rats of salicylic acid with low gastric ulcerogenicity was examined. The distribution and metabolism of the radioactively labelled salicylic acid (SA) was evaluated after oral gavage administration using whole body autoradiography and chemical analyses. Results show that salicylic acid is absorbed as it was rapidly found in blood. Moreover, salicylic acid is distributed in several organs in the body. Qualitative organ distribution of radioactivity : ASA (100 mg/kg): Non glandular mucosa of stomach = kidneys = inflamed paws > lungs > glandular mucosa of stomach = liver = bone marrow = intestine. SA (10 and 100 mg/kg): Non glandular mucosa of stomach = inflamed paws > lungs > liver >= glandular mucosa of stomach = kidneys = bone marrow = intestine.