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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

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Endpoint:
dermal absorption
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: QSAR estimations from dermal absorption tend to be conservative; however, they are not formally validated
Principles of method if other than guideline:
The Danish QSAR Database reports DERMWINv.2 calculations. These are based on the Guy & Potts formula (GUY R.H. AND POTTS R.O., 1992. Structure-Permeability Relationships in Percutaneous absorption. J. Pharm. Sci.. 81: 603-604).
Parameter:
percentage
Absorption:
<= 10 %
Remarks on result:
other: 8 h
Remarks:
Concluded on the basis of the very low predicted absorption rate of 0.00001 mg/cm²/event.
Conclusions:
It is concluded that absorption of PETMP through human skin in vivo within 8 h will be significantly less than 10%. This is a very conservative assumption that will be used for dermal risk assessments.
Endpoint:
basic toxicokinetics
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Expert judgement is combined with the prediction of metabolism provided by the OECD QSAR Application Toolbox.
Objective of study:
toxicokinetics
Principles of method if other than guideline:
No guideline exists for this type of appraisal.
GLP compliance:
no
Species:
other: in silico modelling
Details on test animals or test system and environmental conditions:
not applicable
Route of administration:
other: oral and dermal route are considered
Details on exposure:
not applicable
Type:
absorption
Results:
Oral absorption is predicted to be high. The Danish QSAR database predicts an oral absorption of 95% following a dose of 1 mg. The Danish QSAR database predicts a very low dermal absorption of 0.00001 mg/cm²/event.
Type:
distribution
Results:
The substance will be hydrolysed and the hydrolysis products are very polar and are predicted to have no accumulation potential. They are expected to enter the urine shortly after systemic absorption.
Type:
excretion
Results:
The hydrolysis products of PETMP as well as the oxidised metabolites are very polar and will be excreted rapidly via urine. Faecal excretion is not expected.
Details on absorption:
Oral absorption is predicted to be high. The Danish QSAR database predicts an oral absorption of 95% following a dose of 1 mg. The Danish QSAR database predicts a very low dermal absorption of 0.00001 mg/cm²/event.
Details on distribution in tissues:
The substance will be hydrolysed and the hydrolysis products are very polar and are predicted to have no accumulation potential. They are expected to enter the urine shortly after systemic absorption.
Details on excretion:
The hydrolysis products of PETMP as well as the oxidised metabolites are very polar and will be excreted rapidly via urine. Faecal excretion is not expected.
Metabolites identified:
not measured
Details on metabolites:
PETMP will undergo enzymatic and non-enzymatic ester hydrolysis. The resulting molecules, 3-mercaptopropionate and pentaerythritol, are highly soluble in water. Both substances can be further oxidised (-SH to -SO3H; -CH2OH to -COOH).
Conclusions:
Interpretation of results: no bioaccumulation potential based on study results
PETMP is predicted to be bioavailable via the oral route but is very poorly absorbed via skin.
PETMP is expected to undergo stepwise hydrolysis of the ester bonds yielding 3-mercaptopropionate and pentaerythritol. Concomitant oxidation of the hydrolysis products is likely.
Both substances are very polar and thus subject to renal elimination. Tissue accumulation can be excluded.
Executive summary:

The toxicokinetic behaviour of PETMP [pentaerythritol tetrakis(3-mercaptopropionate)] was assessed. The OECD QSAR Application Toolbox was used to make a qualitative prediction of metabolites formed in liver, skin and gastrointestinal tract.

The Danish QSAR Database was used to predict dermal and oral bioavailability of PETMP.

The fate of these metabolites is predicted on the basis of their chemical structure based on expert judgement.

PETMP is predicted to be bioavailable via the oral route but is very poorly absorbed via skin.

PETMP is expected to undergo stepwise hydrolysis of the ester bonds yielding 3-mercaptopropionate and pentaerythritol. Both substances are very polar and thus subject to renal elimination.

Tissue accumulation can be excluded.

Description of key information

Short description of key information on bioaccumulation potential result: 
PETMP is predicted to be bioavailable via the oral route but is very poorly absorbed via skin.
PETMP is expected to undergo stepwise hydrolysis of the ester bonds yielding 3-mercaptopropionate and pentaerythritol. Both substances are very polar and thus subject to renal elimination. Tissue accumulation can be excluded.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information

No experimental data on absorption, distribution, metabolism and excretion of PETMP are available.

According to REACh, the human health hazard assessment shall consider the toxicokinetic profile (Annex I). However, generation of new data is not required as the assessment of the toxicokinetic behaviour of the substance should be performed to the extent that can be derived from the relevant available information (REACh Annex VIII, 8.8.1).

Qualitative information on toxicokinetic behaviour can be derived taking into account the information on the chemical properties of the compound as well as data obtained in a basic data set.

 

Absorption: Oral absorption is predicted to be high. The Danish QSAR database predicts an oral absorption of 95% following a dose of 1 mg. The Danish QSAR database predicts a very low dermal absorption of 0.00001 mg/cm²/event.

 

Distribution: The substance will be hydrolysed and the hydrolysis products are very polar and are predicted to have no accumulation potential. They are expected to enter the urine shortly after systemic absorption.

 

Metabolism: PETMP will undergo enzymatic and non-enzymatic ester hydrolysis. The resulting molecules, 3-mercaptoproprionate and pentaerythritol, are highly soluble in water. Both substances can be further oxidised (-SH to -SO3H; -CH2OH to -COOH).

 

Excretion: The hydrolysis products of PETMP as well as the oxidised metabolites are very polar and will be excreted rapidly via urine. Significant faecal excretion is not expected.