Sodium 1-(3,4-dihydro-6-methyl-2,4-dioxo-2H-pyran-3-ylidene)ethanolate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Circa 1950

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Dehydroacetic acid (DHA). III. Estimation, absorption, and distribution

Author:

Woods LA, Shideman FE, Seevers MH, Weeks JR & Kruse WT

Year:

1950

Bibliographic source:

J. Pharmacol. Exp. Ther. 99, 84-97

Reference 2

Reference Type:

publication

Title:

Chapter: 4 Final Report on the Safety Assessment of Sodium Dehydroacetate and Dehydroacetic Acid.

Author:

Cosmetic Ingredient Review

Year:

1985

Bibliographic source:

Journal of the American College of Toxicology; 4, No. 3, pp. 123-159,

Materials and methods

Objective of study:

absorption

toxicokinetics

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Basic toxicokinetic study

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione

EC Number:

208-293-9

EC Name:

3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione

Cas Number:

520-45-6

Molecular formula:

C8H8O4

IUPAC Name:

3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione

Specific details on test material used for the study:

Dehydroacetic acid DHA, CAS 520-45-6

Radiolabelling:

no

Test animals

Species:

monkey

Strain:

not specified

Details on species / strain selection:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Duration and frequency of treatment / exposure:

5 days/week for 290-397 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

50 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

200 mg/kg bw/day (nominal)

No. of animals per sex per dose / concentration:

1

Control animals:

not specified

Details on dosing and sampling:

not specified

Statistics:

not specified

Results and discussion

Main ADME results

Type:

absorption

Results:

Peak concentration occurred at 4.5 and 7 days after dosing.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Peak concentration occurred at 4.5 and 7 days after dosing. Plasma levels were 15, 26 to 33, and 45
to 51 mg/100 ml from lowest to highest dosage and diminished rapidly and progressively from high- to
low-dose groups.

Details on distribution in tissues:

not specified

Details on excretion:

not specified precisely

Metabolite characterisation studies

Metabolites identified:

not specified

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

not specified

Applicant's summary and conclusion

Conclusions:

Peak concentration occurred at 4.5 and 7 days after dosing. Plasma levels were 15, 26 to 33, and 45
to 51 mg/100 ml from lowest to highest dosage.
Olive oil had no apparent effect on absorption.

Executive summary:

Monkeys (2 per dose group) received oral doses of 50, 100, and 200 mg/kg bw/day, 5 days per week,

for 290 to 397 days. Dehydroacetic Acid was administered in olive oil to 1 monkey in each group.

Plasma concentrations of Dehydroacetic Acid were determined at various intervals after dosing. The

peak concentration occurred between 4.5 and 7 hours after dosing (plasma levels at 4 hours from low

dose to high were 15, 26 to 33, and 45 to 51 mg/l00 ml, respectively), and diminished rapidly and

progressively from high- to low-dose groups. Olive oil apparently had no influence on absorption.