4-hydroxybenzoic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

in 1952 or earlier

Reliability:

other:

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

acceptable, according to the standards of the time well-documented study which meets basic scientific principles Results are reported for 4-HBA and the read across substance Methylparaben also. For detailed read across justification please refer to the read across rationale attached to this endpoint study record. It is also attached to section 13 of iuclid as Appendix to the Chemical Safety Report. Data of methylparaben and ethylparaben can be taken for the evaluation of 4-HBA as there is a close structural similarity and the fact that 4-HBA is the main breakdown product of the precursor methylparaben and ethylparaben after oral and other routes of administration. Justification for read-across: similar chemical structure (common functional group) and common precursors and/or the likelihood of common breakdown products via physical and biological processes, which result in structurally similar chemicals. (For detailed read across justification please refer to the read across rationale attached to this endpoint study record. It is also attached to section 13 of iuclid as Appendix to the Chemical Safety Report.)

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1956

Report date:

1956

Materials and methods

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

p-hydroxybenzoic acid

IUPAC Name:

p-hydroxybenzoic acid

Details on test material:

- Name of test material (as cited in study report): p-hydroxy-benzic acid, PHBA

A second substance was tested in comparison:
- Name of test material (as cited in study report): Methyl p-hydroxy-benzoate
- Substance type: ester
THE FOLLOWING DATA ARE NOT STATED IN THE REPORT:
- Molecular formula (if other than submission substance): C8H8O3
- Molecular weight (if other than submission substance): 152.16
- CAS number: 99-76-3
- EC number: 202-785-7
- IUPAC name: Methyl-4-hydroxy benzoate
- Physical state: solid

Test animals

Species:

dog

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: capsule

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

single administration of 4-HBA and Methyl paraben

Doses / concentrations

Remarks:

Doses / Concentrations:
1.0 g/kg bodyweight each.

No. of animals per sex per dose / concentration:

3

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood,urine
- Time and frequency of sampling: 5, 15 and 30 min, 1, 2, 4, 6, 12, 24 and 48 hours
- From how many animals: 3
- Method type for identification: spectrometric

Statistics:

Average of 3 dogs

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Absorption is essentially complete as 94 % of pHBA of initial dose were recovered in urine.

Details on excretion:

An oral dosage of 4-HBA and Methyl paraben resulted in the same plasma levels of 4-HBA.
94% of an oral dosage of 1.0 g 4-HBA/kg bodyweight to dogs were recovered in the urine, 40.1% as free 4-HBA, 30.0% as glucuronic acid-conjugate. 89% of an oral dosage of 1.0 g methyl paraben/kg body weight to dogs were recovered in the urine, 21.3% as free 4-HBA, 35.1% as glucuronic acid-conjugate.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Oral dosages of 1.0 g/kg bodyweight of 4-HBA/Methyl paraben were given to groups of 3 dogs, respectively. After administration of 4-HBA and Methyl paraben the same concentrations of free 4 -HBA and the same kinetics for the elimination of 4 -HBA were found in the plasma. After the oral administration of 4 -HBA 94% of the dosage were recovered in the urine, 40.1% as free 4-HBA, 30.0% as glucoronide acid conjugate.
After the oral administration of Methyl paraben 89% of the dosage were recovered in the urine, 21.3% as free 4-HBA, 35.1% as glucoronide acid conjugate.

Applicant's summary and conclusion

Conclusions:

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

Executive summary:

Oral dosages of 1.0 g/kg bodyweight were given to groups of 3 dogs. After administration of 4-HBA and Methyl paraben the same concentrations of free 4 -HBA and the same kinetics for the elimination of 4 -HBA were found in the plasma.

After the oral administration of 4 -HBA 94% of the dosage were recovered in the urine, 40.1% as free 4-HBA, 30.0% as glucoronide acid conjugate.

After the oral administration of Methyl paraben 89% of the dosage were recovered in the urine, 21.3% as free 4-HBA, 35.1% as glucoronide acid conjugate.

Obviously methyl paraben is quickly degraded to 4 -HBA in the stomach.