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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given.

Data source

Reference
Reference Type:
publication
Title:
Métabolisme d'un Conservateur Alimentaire: L'Acide Parahydroxybenzoïque et ses Esters
Author:
Derache, R. and Gourdon, J.
Year:
1963
Bibliographic source:
Fd Cosmet. Toxicol. 1, 189-195

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
Investigation of toxicokinetics and elimination of p-hydroxybenzoic acid and its esters in Wistar rats.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: no data
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: approximately 200 g
- Individual metabolism cages: yes

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Duration and frequency of treatment / exposure:
single treatment and an observation period of up to 6 h in metabolism cages
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg/rat (corresponding to approximately 500 mg/kg bw)
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, blood
- Time and frequency of sampling: Sampling started directly after dosing and was perfomred up to 6 hours after test substance administration.

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: Sampling started directly after dosing and was perfomed every 30 min up to 6 hours after test substance administration.
- Method type(s) for identification: paper chromatography (qualitative); quantification was done using spectrometry.

TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable): heating with HCl at 110 °C for various time periods

Results and discussion

Main ADME resultsopen allclose all
Type:
metabolism
Results:
identified metabolites were p-hydroxybenzoic acid, p-hydroxyhippuric acid, conjugates with glucuronic acid, ethereal sulphate and an unidentified metabolite
Type:
excretion
Results:
rapid urinary excretion starting directly after administration

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Free p-hydroxybenzoic acid is immediately excreted via urine after absorption, reaching a maximum after 90 min. Renal excretion of p-hydroxyhippuric acid starts after ca. 30 min and constantly increases up to 4 h after ingestion. Conjugates with glucuronic acid appear in the urine between 30 and 75 min after administration, also reaching an excretion maximum after 4 h.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
In the urine of treated rats, p-hydroxybenzoic acid, p-hydroxyhippuric acid and conjugates with glucuronic acid were detected within 4 h after application.

Any other information on results incl. tables

The blood concentration of p-hydroxybenzoic acid reaches a maximum after 30 min after administration giving a plateau after ca. 2 h. The blood concentration of propyl-4-hydroxybezoate reaches its maximum approx. 30 min after oral administration and then constantly declines.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results