Phosphorous acid, mixed 2,4-bis(1,1-dimethylpropyl)phenyl and 4-(1,1-dimethylpropyl)phenyl triesters

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

10

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

10

Additional information

Inhalation

No specific studies on inhalation of the substance itself are available. As the substance is known to be minimally absorbed from the ADME studies, and given that the vapour pressure of DVS005u is not sufficiently volatile to indicate that this is a route of exposure, as a worst case, 10% inhalation absorption default is assigned.

 

Dermal

Chapter R.7c: Endpoint specific guidance details as follows:

Substances that can potentially be taken up across the skin include gases and vapours, liquids and particulates. A tiered approach for the estimation of skin absorption has been proposed within a risk assessment framework (EC, 2007): Initially, basic physico-chemical information should be taken into account, i.e. molecular mass and lipophilicity (log P). Following, a default value of 100% skin absorption is generally used unless molecular mass is above 500 and log P is outside the range [-1, 4], in which case a value of 10% skin absorption is chosen (de Heer et al., 1999).

The substance has the following parameters:

MW range of 520 - 731;

Water solubility: < 0.1 mg/l

Log Kow: 6.58 ± 0.32.

 

Taking account of the details within Table R.7.12—3 Interpretation of data regarding dermal absorption, a dermal absorption of 10% is proposed, based on the guidance. This is reinforced by the fact that the oral absorption rate is approximately 10% and is considered appropriate.

 

Oral

Oral absorption of DVS005 (Weston 705T) was found to be low (range 4.01 to 7.75%) although this was higher after repeated administration compared with a single dose. Of this, urinary excretion represented the major component (range 3 to 6%). Altogether 9 metabolites, all below 5% of the administered dose, were found in the urine.

Faecal elimination accounted for 81 to 92% on the radioactivity in both males and females after 48 hours, for respectively the low and high dose group. In the repeated dose group (100 mg/kg) the faecal elimination was slightly lower compared with the single dose groups. Since no metabolites were found in the faeces it was considered that this material represented unabsorbed material.

At termination of the study, the average total remaining radioactivity in blood, carcass plus tissues was between 0.397 and 0.844% of the administered dose after oral dosing. The mean percentage of radioactivity in the carcass was 0.122-0.157%.

As a worst case, an oral absorption of 10% is proposed.