Phenyl bis(2,4,6-trimethylbenzoyl)-phosphine oxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: assessment

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: toxicokinetics assessment was completed according to ECHA Guidance on information requirements and chemical safety assessment, Chapter R.7c, R.7.12 Guidance on Toxicokinetics (2008)

Data source

Reference

Reference Type:

other: assessment report

Title:

Unnamed

Year:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: ECHA guidance on information requirements and chemicalsafety assessment, Chapter R.7c: Endpoint specific guidance, R.7.12 Guidance on Toxicokinetics, May 2008

Deviations:

not applicable

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenyl bis(2,4,6-trimethylbenzoyl)-phosphine oxide

EC Number:

423-340-5

EC Name:

Phenyl bis(2,4,6-trimethylbenzoyl)-phosphine oxide

Cas Number:

162881-26-7

Molecular formula:

C26H27O3P

IUPAC Name:

[phenyl(2,4,6-trimethylbenzoyl)phosphoryl](2,4,6-trimethylphenyl)methanone

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral/Gastrointestinal(GI) absorption:
The acute oral toxicity data showing the LD50 > 2000 mg/kg bw/day indicated that no signs of systemic toxicity is present. Clinical signs were confined to piloerection, seen in all rats and recovery was complet by Day 3. In the repeated dose toxicity study (28 day) there was no clinical observation noted that could be indicative of treatment to the substance. One female died in week 1 of an intubation error. Laboratory findings showed limited absorption took place orally. Since the substance is insoluble in water and has relatively large particle size, it is considered to have low oral/GI absorption.

Inhalation absorption:
As substance is insoluble in water, has low volatility and low vapour pressure, it is expected that it has no or very limited potential to be inhaled.

Dermal absorption:
The substance is considered to have dermal absorption because it has been identified as a skin sensitizer according to CLP Regulation. With a log P value of between 4 and 6, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Since cells in the outer layer (e.g. stratum corneum is the outermost layer of the eqidermis) are resistant to chemicals, also there are no blood vessels in the outer layer as well as there is no evidence of systemic toxicity reported in the 28-day oral toxicity study of the substance (Effects in organs: No treatment-related gross or microscopic changes were observed.), it is to be expected that uptake into the stratum corneum is probably but the chemical will not manage to pass through the outer skin layer and therefore, it will not pass through the rest of the skin and not enter the circulation.

Details on distribution in tissues:

System effect were not observed in the 28-day oral toxicity study. It is therefore possible to conclude that the substance is not transported. As a highly lipophilic substance, substance may penetrate the skin but probably reach the stratum corneum and is not well absorbed systemically because of no evidence of systemic toxicity records. After dermal absorption, this chemical may persist in the stratum corneum, but it will eventually be cleared as the stratum corneum is sloughed off. Accumulation in fat or in other tissues is unlikely.

Details on excretion:

The route of excretion for the substance is exfoliation. As a highly lipophilic subbstance which has penetrated the stratum corneum but not penetrated the viable epidermis, the chemical may be sloughed off with skin cells.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

In view of its hydrophobicity, high lipophilic (log P between 4 and 6), low volatility and large particle size, oral and inhalation absorption of the substance are considered negligible. There is sufficient evidence that dermal absorption takes place and uptake into the stratum corneum will be high. In the case dermal absorption occurs, substance that have penetrated the stratum corneum but not penetrated the viable epidermis may be sloughed off with skin cells. Accumulation in the body during prolonged exposure will be very low.