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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECD guideline or GLP defined.

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1987

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
effects of i.p. injection on toxicokinetics in rats
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 3-methylphenyl diphenyl phosphate, 4-methylphenyl diphenyl phosphate, bis(3-methylphenyl) phenyl phosphate, 3-methylphenyl 4-methylphenyl phenyl phosphate and triphenyl phosphate
EC Number:
945-730-9
Molecular formula:
3-methylphenyl diphenyl phosphate: C19H17O4P 4-methylphenyl diphenyl phosphate´: C19H17O4P triphenyl phosphate: C18H15O4P bis(3-methylphenyl) phenyl phosphate: C20H19O4P 3-methylphenyl 4-methylphenyl phenyl phosphate: C20H19O4P
IUPAC Name:
Reaction mass of 3-methylphenyl diphenyl phosphate, 4-methylphenyl diphenyl phosphate, bis(3-methylphenyl) phenyl phosphate, 3-methylphenyl 4-methylphenyl phenyl phosphate and triphenyl phosphate
Details on test material:
A commercial cresyl diphenyl phosphate preparation was analysed to contain approximately 35% of triphenyl phosphate, 45% of cresyl diphenyl phosphates, 18% of dicresyl phenyl phosphates and 2% of tricresyl phosphates.
Radiolabelling:
not specified

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
olive oil
Duration and frequency of treatment / exposure:
single injection i.p.
Doses / concentrations
Remarks:
Doses / Concentrations:
75, 150 or 300 mg/kg
No. of animals per sex per dose / concentration:
5
Control animals:
not specified

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data
Details on distribution in tissues:
4 hours after the intraperitoneal injection of 300 mg test substance the Diphenyl-cresyl-phosphate level in blood was 0.3 +/- 0.2 µg/g. After 24 hours the level was below the detection limit (0.2 µg/g). In the liver the concentrations after 4 hours were 45.8 +/- 28.1 µg/g tissue and after 24 h 1.7 +/- 2.5 µg/g.
Details on excretion:
no data
Toxicokinetic parameters
Toxicokinetic parameters:
other: 4 h after the i.p. injection of 300 mg test subst. the DPK level in blood was 0.3 +/- 0.2 µg/g. After 24 h the level was below the detection limit (0.2 µg/g). In liver the conc. after 4 hours were 45.8 +/- 28.1 µg/g tissue and after 24 h 1.7 +/- 2.5 µg/g.

Metabolite characterisation studies

Metabolites identified:
not specified

Any other information on results incl. tables

Concentrations of Triarylphosphates in rat liver and blood 4 and 24 h after intraperitoneal injektion (300 mg/kg) of commercial cresyl diphenyl phosphate:

The concentrations are in µg/g wet tissue (mean of 5 animals +/- S.D.). The detection limit is 0.2 µg/g).

 Time after treatment  TPP CDPP  DCPP  TCP 
 Liver        
 4h 36.6 +/- 23.3  45.8 +/- 28.1  24.0 +/- 15.8  3.5 +/-2.8 
 24 h 1.8 +/- 1.9  1.7 +/- 2.5  1.4 +/- 1.1  < 0.2 
 Blood        
 4h 0.7 +/- 0.3  0.3 +/- 0.2   < 0.2   < 0.2
             No detectable amounts were found in blood 24 h after injection.

TCP- tricresyl phosphates.

TPP-triphenyl phosphate

CDPP- cresyl diphenyl phosphates DCPP- dicresyl phenyl phosphates TCP- tricresyl phosphates.

Applicant's summary and conclusion

Executive summary:

In a toxicokinetic study male Wistar rats (250 -300g) were injected intraperitoneally with 75, 150 or 300 mg/kg of a commercial triaryl phosphate preparation (Disflamoll DPK/25E, Bayer AG, F.R.G.) which was analysed to contain approximately 35% of triphenyl phosphate, 45% of cresyl diphenyl phosphates, 18% of dicresyl phenyl phosphates and 2% of tricresyl phosphates, in olive oil. The animals were decapitated 4h, 24 h, 1 week or 2 weeks after the injections and their brain, blood, liver, kidneys, glutea muscle and tail nerve samples were taken at autopsy.

4 hours after the intraperitoneal injection of 300 mg test substance the Diphenyl-cresyl-phosphate level in blood was 0.3 +/- 0.2 µg/g. After 24 hours the level was below the detection limit (0.2 µg/g). In the liver the concentrations after 4 hours were 45.8 +/- 28.1 µg/g tissue and after 24 h 1.7 +/- 2.5 µg/g.