Biphenyl-4,4'-diyl tetraphenyl bis(phosphate)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well documented expert statement based on a series of physicochemical, environmental and toxicology studies with ADK STAB FP-800 and one study with its substance analogue source chemical, EC No. 425-220-8, in general performed according to technical guidelines and in compliance with GLP in internationally recognized contract research organizations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Expert statement based on a series of physicochemical, biodegradation, ecotoxicological and toxicology studies with ADK STAB FP-800 and one reproductive/developmental toxicity screening test with the substance analogue source chemical, EC No. 425-220-8, (read across). Technical guidelines followed in these experimental studies are cited in the respective endpoint study records.

GLP compliance:

no

Remarks:

Considered unnecessary for expert statement

Test material

Test material information

Constituent 1

Reference substance name:

4'-[(diphenoxyphosphoryl)oxy]-[1,1'-biphenyl]-4-yl diphenyl phosphate

EC Number:

700-627-6

Cas Number:

17270-01-8

Molecular formula:

C36H28O8P2

IUPAC Name:

4'-[(diphenoxyphosphoryl)oxy]-[1,1'-biphenyl]-4-yl diphenyl phosphate

Details on test material:

- Name of test material: ADK STAB FP-800
Further details on the test material used in the experimental studies referred to are presented in the respective endpoint study records.

In addition, one study referred to in the present expert statement was a read across from the substance analogue EC No. 425-220-8.

Radiolabelling:

no

Test animals

Species:

other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement

Strain:

other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement

Sex:

male/female

Details on test animals or test system and environmental conditions:

Detailed in the endpoint study records of in-vivo studies referred to in the present expert statement.

Administration / exposure

Route of administration:

other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement

Vehicle:

other: Detailed in endpoint study records of in-vivo and in-vitro studies referred to in the present expert statement, if appropriate

Details on exposure:

Detailed in endpoint study records of in-vivo and in-vitro studies referred to in the present expert statement.

Duration and frequency of treatment / exposure:

Detailed in endpoint study records referred to in the present expert statement.

Doses / concentrations

Remarks:

Doses / Concentrations:
Detailed in endpoint study records of in-vivo and in-vitro studies referred to in the present expert statement.

No. of animals per sex per dose / concentration:

Detailed in endpoint study records of in-vivo studies referred to in the present expert statement.

Control animals:

other: Detailed in endpoint study records referred to in the present expert statement, if applicable

Positive control reference chemical:

Detailed in endpoint study records referred to in the present expert statement, if applicable

Details on study design:

Detailed in endpoint study records referred to in the present expert statement, if applicable

Details on dosing and sampling:

Detailed in endpoint study records referred to in the present expert statement, if applicable

Statistics:

Detailed in endpoint study records referred to in the present expert statement, if applicable. Not applicable for the present expert statement.

Results and discussion

Preliminary studies:

Not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The rather high molecular weight (650.6), low water solubility < 0.01 mg/L at 20°C) and high lipophilicity (Log10Pow = 5.5 at 25°C) of ADK STAB FP-800 would be expected to limit its absorption across the skin after topical administration and to limit its absorption after oral administration [ECHA 2008, Chapter R.7c: Endpoint specific guidance]. Consequently the above physicochemical properties of ADK STAB FP-800 are considered to limit its systemic availability both, after topical and after oral administration. This is consistent with the absence of relevant signs of irritation in an acute dermal toxicity study in the rat, skin and eye irritation studies in the rabbit and a Local Lymph Node Assay (LLNA) in mice and with the absence of any sensitization response in the latter study. All of these studies were conducted with ADK STAB FP-800. In addition, in a repeat dose oral toxicity study (OECD 407), in which rats received ADK STAB FP-800 at 25, 150 or 1000 mg/kg/day on 28 consecutive days, findings indicative of absorption or systemic exposure were not evident after 4 treatment weeks and also not after a subsequent 2-week treatment free recovery period. Also the structural substance analogue source chemical, EC No. 425-220-8, did not induce any signs of absorption in rats dosed up to and including 1000 mg/kg/day for 28 to 46 days in a reproductive/developmental toxicity screening test (OECD 421).

From the absence of any toxicity in all of these studies and the absence of any relevant adverse effects in in-vitro genotoxicity tests or on algae, daphnia, fish or bacteria in ecotoxicology studies, and from ADK STAB FP-800 being not readily biodegradable and not predicted as oxidising, it is concluded that ADK STAB FP-800 may behave quasi-inert in biological systems. Relevant bioaccumulation was not evident in a bioaccumulation study in fish.

No data is available on absorption after inhalation. Inhalation of any vapour from ADK STAB FP-800 is an unlikely route of human exposure, because the substance has a very low vapour pressure (5.3 x 10E-5 Pa at 25°C) and decomposes without boiling at high temperatures (≥ ca. 260°C). Exposure of humans to an inhalable aerosol of ADK STAB FP-800 is also unlikely, because the vast majority of it comprises flakes and particulate material > 100 µm generally regarded as not inhalable by humans (98.0 mass % of the particles of ADK STAB FP-800 > 125 µm, 2.1% ≤ 125 µm > 75 µm and 0% ≤ 75 µm). In view of the absence of any particles ≤ 75 µm, the small portion of possibly inhalable particles predominantly will settle in the nasopharyngeal region. The high molecular weight (650.6) and low water solubility (< 0.01 mg/L) of ADK STAB FP-800 lower the potential for absorption. In the liquid form FP-800 is very viscous in addition limiting its availability as inhalable aerosol. Thus, also after inhalation, ADK STAB FP-800 may behave rather like inert material with low systemic availability.

Details on distribution in tissues:

There is no indication in the available study results regarding the metabolism or distribution of ADK STAB FP-800 or components thereof.

Details on excretion:

There is no indication in the available study results regarding the excretion of ADK STAB FP-800 or components thereof.

Metabolite characterisation studies

Metabolites identified:

not specified

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
No specific study was performed on the absorption, distribution, metabolism and/or excretion (ADME) of ADK STAB FP-800. Its absorption and systemic availability after topical or oral administration is expected to be limited, because of its high molecular weight, low water solubility and high lipohilicity and because of the absence of relevant toxicity findings in all available toxicity studies. Availability of ADK STAB FP-800 under a vapour state is unlikely, because of its low vapour pressure.

Quasi-inert behaviour of ADK STAB FP-800 in biological systems has been inferred from the absence of relevant toxicity in all available toxicology studies and the absence of adverse effects on algae, daphnia, fish or bacteria in ecotoxicology studies, and from ADK STAB FP-800 being not readily biodegradable in a standard laboratory test and not predicted as oxidising.

All available study results gave no indication regarding the metabolic pathway, distribution or excretion of ADK STAB FP-800. Bioaccumulation was not investigated in mammals, but in fish it was not evident.

Based on all available information it is concluded that ADK STAB FP-800 has no potential for bioaccumulation.