3-mercaptopropionic acid

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

dermal absorption

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

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).

Conclusions:

MPA is predicted to have significant dermal absorption potential. SInce MPA is highly corrosive, dermal exposure must be prevented by suitable protective garment.

Reference 2

Endpoint:

basic toxicokinetics in vitro / ex vivo

Remarks:

plasma protein binding

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Because of the chemical properties of PETMP and 3-MPA it was necessary to develop two separate LC-MS/MS methods. The run time is for both methods < 10 minutes. The working range for PETMP is 10 – 1000 ng/mL and for 3-MPA 50 – 1000 ng/mL.

GLP compliance:

no

Remarks:

preliminary study

Conclusions:

The aim of this study was the method development for the determination of PETMP and its metabolite 3-MPA in rat plasma by LC-MS/MS. For this purpose, at first a LC-MS/MS method was developed for both analytes and two different protein precipitation methods were tested for the extraction.
The analysis for both components PETMP (main component) and 3-MPA (hydrolysis product) can not be conducted with one LC-MS/MS method. Extraction experiments indicate the sorption of both analytes to plasma proteins which would also occur in the organism. Strong protein binding is postulated (e.g. to cysteine) and well known for substances with mercapto-groups.

Reference 3

Endpoint:

basic toxicokinetics

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2009

Reliability:

2 (reliable with restrictions)

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: not applicable

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

Details on absorption:

MPA is predicted to be moderately bioavailable (50%) via the oral route and readily absorbed via skin.

Details on distribution in tissues:

MPA and its metabolites are very polar and are predicted to have no accumulation potential. They are expected to be enter the urine shortly after systemic absorption.

Details on excretion:

MPA 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:

MPA is expected to undergo stepwise oxidation of the thiol group yielding 3-sulfinopropanoic acid and 3-sulfopropanoic acid. Both substances are very polar and thus subject to renal elimination.
In addition, disulphide bridge formation with cysteine or with another MPA molecule may occur.

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
MPA is predicted to be moderately bioavailable (50%) via the oral route and readily absorbed via skin.
MPA is expected to undergo stepwise oxidation of the thiol group and also disulphide bridge formation with cysteine or with another MPA molecule.
MPA and its metabolites are very polar and thus subject to renal elimination. Tissue accumulation can be excluded.

Executive summary:

The toxicokinetic behaviour of MPA [3-mercaptopropionic acid] 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 MPA.

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

MPA is predicted to be moderately bioavailable (50%) via the oral route and readily absorbed via skin.

MPA is expected to undergo stepwise oxidation of the thiol group yielding 3-sulfinopropanoic acid and 3-sulfopropanoic acid. Both substances are very polar and thus subject to renal elimination.

In addition, disulphide bridge formation with cysteine or with another MPA molecule may occur.

Tissue accumulation can be excluded.

Description of key information

Short description of key information on bioaccumulation potential result: 
MPA is predicted to be moderately bioavailable (50%) via the oral route and readily absorbed via skin.
MPA is expected to undergo stepwise oxidation of the thiol group and also disulphide bridge formation with cysteine or with another MPA molecule. MPA and its metabolites are very polar and thus subject to renal elimination. Tissue accumulation can be excluded.

Additional information

Absorption

Oral absorption of MPA is predicted to be moderate. The Danish QSAR database predicts an oral absorption of 50% following a dose of 1 mg.

The Danish QSAR database predicts a high dermal absorption of 0.089 mg/cm²/event. It is noteworthy that MPA is highly corrosive, so that contact with skin must be thoroughly prevented. 

Distribution

MPA and its predicted oxidation products are very polar and are predicted to have no accumulation potential. They are expected to enter the urine shortly after systemic absorption.

Metabolism

MPA will undergo enzymatic and non-enzymatic ester oxidation of its thiol group. This is a stepwise process. It is predicted that MPA can also be oxidised to form disulphide bridges either with itself (dimerisation) or with cysteine, either in glutathione or in proteins. The latter process may promote skin sensitisation.