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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
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

Referenceopen allclose all

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 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

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
200 mg/kg bw/day (nominal)
No. of animals per sex per dose:
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

Bioaccessibility 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.