[No public or meaningful name is available]

Basic toxicokinetics

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

Test material information

Constituent 1

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

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.