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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: It is well documented and scientifically acceptable. Also assessed by OECD.

Data source

Reference
Reference Type:
publication
Title:
Metabolism of Phosphoric Acid Triesters by Rat Liver Homogenate
Author:
Sasaki K, Suzuki T, Takeda M, Uchiyama M
Year:
1984
Bibliographic source:
Bull Environ Contam Toxicol 33 (3), 281-288

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
Method: C36-001:
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
Rats used weighed between 150-200g.

Administration / exposure

Control animals:
yes, concurrent no treatment
Details on study design:
Rat livers were removed and the microsomal and soluble fractions extracted. An ethanol solution of TPP at 0.0004M was used as substrate to determine the extent of decomposition by the fractions with and without NADPH and other enzyme systems. Major metabolites resulting from TPP degradation were characterised using gas chromotography.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
half-life 2nd:
Toxicokinetic parameters:
half-life 1st:
Toxicokinetic parameters:
half-life 3rd:

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Diphenyl phosphate (DPP) was the only major metabolite of TPP.

Applicant's summary and conclusion

Conclusions:
TPP is degraded by hydrolysis in rat liver homogenate to diphenyl phosphate (DPP) as the major product.
Executive summary:

Investigation to obtain basic data on the metabolic transformation of TPP, the decomposition of TPP in vitro by rat liver preparation was examined and the effects of coenzymes and inhibitors on the metabolism were investigated to elucidate the predominant enzyme reaction involved. The results showed that TPP was decomposed to diphenyl phosphate (DPP) by both MFO and arylesterase in microsomes.